Role of pituitary hormones in regulating renal vitamin D metabolism in man.

Studies in animals and tissue culture have shown the importance of prolactin and growth hormone in regulating renal 1 alpha-hydroxylase activity and plasma concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)2D3). Evidence for a similar role for these hormones in man was sought by using a radioreceptor assay to measure plasma 1,25(OH)2D3 concentrations in 20 normal subjects, 12 patients receiving dialysis, 11 patients with primary hyperparathyroidism, 10 pregnant women, seven women with prolactinoma, and 14 patients with acromegaly. Circulating 1,25(OH)2D3 concentrations were appreciably raised in the patients with primary hyperparathyroidism and the pregnant women (P less than 0.001), slightly but significantly increased in the patients with prolactinoma (P less than 0.05), and greatly raised in those with acromegaly (P less than 0.001). These results suggest that prolactin and growth hormone are important regulators of renal vitamin D metabolism in the physiological conditions of pregnancy, lactation, and growth in man.     

Role of vasoactive intestinal polypeptide (VIP) in regulating the pituitary function in man

Intramuscular injection of synthetic VIP (200 micrograms) resulted in a rapid increase in plasma prolactin (PRL) concentrations in normal women, which was accompanied by the 4- to 7-fold increase in plasma VIP levels. Mean (+/- SE) peak values of plasma PRL obtained 15 min after the injection of VIP were higher than those of saline control (28.1 +/- 6.7 ng/ml vs. 11.4 +/- 1.6 ng/ml, p less than 0.05). Plasma growth hormone (GH) and cortisol levels were not affected by VIP in normal subjects. VIP injection raised plasma PRL levels (greater than 120% of the basal value) in all of 5 patients with prolactinoma. In 3 of 8 acromegalic patients, plasma GH was increased (greater than 150% of the basal value) by VIP injection. In the in vitro experiments, VIP (10(-8), 10(-7) and 10(-6) M) stimulated PRL release in a dose-related manner from the superfused pituitary adenoma cells obtained from two patients with prolactinoma. VIP-induced GH release from the superfused pituitary adenoma cells was also shown in 5 out of 6 acromegalic patients. VIP concentrations in the CSF were increased in most patients with hyperprolactinemia and a few cases with acromegaly. These findings indicate that VIP may play a role in regulating PRL secretion in man and may affect GH secretion from pituitary adenoma in acromegaly.     

Clinical studies on thyroidal autoantibodies.

In an attempt to clarify autoimmune nature of Grave's disease and Hashimoto's thyroiditis, thyroidal autoantibodies have been studied on 86 cases of Grave's disease, 54 cases of Hashimoto's thyroiditis, 31 cases of simple goiter, 11 cases of primary hypothyroidism a-d 22 cases of thyroid neoplasia as well as on 364 healthy subjects. Two kinds of tanned red cell hemagglutination tests were carreid out on each case. One method using refined human thyroglobulin for sensitization of sheep red cells has been found to be specifice for anti-thyroglobulin antibody and to be frequently positive in Hashimoto patients. However, in another method using human thyroidal microsomes (purified by ultracentrifugation) as sensitizing antigen, some heterogenous antibodies including anti-thyroglobulin antibody might be detected together with the antibody against the antigen proper to thyroidal micorsome (HF antigen)which is derived from hyperfunctioning thyroidal follicular cells of Grave's patients. hAnti-HF antibody is frequently detected both in Hashimoto and Grave's patients. In other thyroid diseases the titers of both thyroidal autoantibodies were generally low, though higher than in healthy subjects. The effect of aging on thyroidal autoantibodies in healthy subjects was clearly observed in females but not in males. From the results of these two test, it is possible to speculate that high=columnar and hyperfunctioning thyroidal follicular cells might exist focally in most cases of Hashimoto's thyroiditis.     

Increased plasma VIP concentration in patients with prolactinoma.

Vasoactive intestinal polypeptide (VIP) is now considered to be a prolactin-releasing factor (PRF). The aim of this study was to determine the VIP concentration in peripheral blood in patients with prolactin-secreting adenoma compared to healthy subjects. We also examined the effect of bromocriptine administration on the plasma VIP concentration in patients with prolactinoma. Nine patients with prolactinoma (6 women and 3 men, aged 27-50) and 7 healthy control subjects (4 women and 3 men, aged 26-40) were examined. Blood samples for prolactin and VIP were collected at 06:00, 12:00, 18:00, 24:00. In prolactinoma blood was taken before and after bromocriptine administration. Serum prolactin concentration was determined by the radioimmunoassay. VIP concentration was measured by a specific radioimmunoassay Kit-INCSTAR Corp. (Minnesota, USA). Statistical significance was calculated using the analysis of variance. A single 5 mg oral dose of bromocriptine decreased the mean prolactin concentration during the first 24 hours of treatment. Plasma VIP concentration was higher in prolactinoma patients compared to healthy subjects. There was no change in plasma VIP level after bromocriptine administration. In conclusion: in patients with prolactin secreting adenoma the plasma VIP concentration is increased.     

Autoimmune recognition of thyroglobulin and thyroid hormones in rabbits

Two rabbits (RG-1, RG-2) were immunized with rabbit thyroglobulin (RTg) purified from thyroid glands of four other normal rabbits of the same strain, and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. Production of anti-RTg as well as anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed in both rabbits. Physicochemical parameters of anti-RTg antibodies with RTg, T4, and T3 were calculated in two selected antisera (70-day and 253-day) of each of the rabbits, using a Scatchard plot. Extraction of serial sera from both rabbits disclosed the presence of larger amounts of T3 and T4 in immune sera than in preimmune serum. Examination of pathology of thyroid glands and kidneys in both rabbits was negative for the lesions of autoimmune thyroiditis and immune nephritis. These results indicate that anti-Tg as well as anti-thyroid hormone autoantibodies can be raised without thyroid pathology in rabbit by immunization with autologous Tg.     

Occurrence of various autoantibodies in autoimmune diseases

The study aimed at determining the incidence of autoantibodies occurrence in the course of autoimmunological diseases of the thyroid gland and in healthy population. Autoantibodies against various structures were assayed, including: cellular nuclei, smooth muscles, mitochondria, biliary tubules, parietal cells, reticular fibres, striated muscles as well as thyroglobulin and thyroid microsomes. The study involved 63 patients with autoimmunological diseases of the thyroid gland (35 patients with Graves-Basedow disease and 28 patients with Hashimoto's disease) and 30 healthy individuals. Thyroid antimicrosomal and antithyroglobulin antibodies were assayed with RIA in stable phase whereas the remaining antibodies--with multifunctional indirect immunofluorescence test. The obtained results are the following: antimicrosomal antibodies were present in 68.3% cases while antithyroglobulin antibodies in 76.2% of the examined patients with autoimmunological diseases of the thyroid gland. Immunofluorescence tests performed in the same group have shown antinuclear antibodies in 13% of cases, antibodies against smooth muscles in 28.6%, antimitochondrial antibodies in 1.6%, antibodies against biliary tubules in 3.4%, antibodies against parietal cells in 11.1%, antibodies against reticular fibres in 7.9%, and antibodies against striated muscles in 9.5% of cases. Antinuclear antibodies, antibodies against smooth muscles, and antibodies against both thyroidal microsome and thyroglobulin (in 3.3%) were the only antibodies found in the control group.     

A comparative study between individuals receiving thymic irradiation in infancy and their nontreated siblings: clinical and laboratory thyroid abnormalities

While impairment of thyroid function has been demonstrated for high-dose external radiation (e.g., for Hodgkin's disease), the long-term functional effects of low-dose external radiation have not been fully explored. One hundred fifty-three subjects with a past history of thymic irradiation during infancy were stratified into three dose levels and compared with 51 nonirradiated subjects from a sibling cohort with respect to previously undiagnosed clinical and laboratory thyroidal abnormalities. There was no apparent association between previous thymic irradiation and mean serum levels of T4, free T4, TSH, or antithyroid antibodies, nor was the prevalence of undetected hypothyroidism or hyperthyroidism significantly altered in the irradiated group. Serum thyroglobulin levels were elevated in subjects with palpable thyroid nodules, all of which occurred in thymic-irradiated subjects. Thus persons who have received low-level external thymic irradiation in infancy should continue to have periodic thyroid examinations, but routine serial measurement of other serum thyroidal parameters does not appear to be indicated.     

Elevated prolactin to cortisol ratio and polyclonal autoimmune activation in Hashimoto's thyroiditis.

Cortisol and prolactin, which are considered to have an immunomodulatory effect, and selected autoantibodies were determined in Hashimoto's thyroiditis. 37 patients (8 males and 29 females) (54 +/- 13.8 years) and an equal number of sex- and age-matched normal subjects (52.6 +/- 14.2 years) were studied. None of the 74 subjects suffered from any other immunological, infectious, hepatic, renal or malignant diseases. Patients with Hashimoto's thyroiditis exhibited significantly higher (p < 0.016) prolactin values (14.0 +/- 3.8 ng/ml) than did control subjects (6.5 +/- 1.3 ng/ml). In contrast, cortisol levels were lower in Hashimoto's thyroiditis (13.5 +/- 3.2 microg/dl) vs. normal state (16.0 +/- 1.13 microg/dl), (p < 0.05). The prevalence of anti-TPO and anti-Tg antibodies was 100 % and 43 % in the patients with Hashimoto's disease. In contrast, no subject of the control group was positive for anti-TPO, although 9 subjects (24 %) were positive for anti-Tg autoantibodies. The percentage of positive autoantibodies to nucleus, smooth-muscle, and parietal cells in the patients (36.0, 10.9 and 18.5 %, respectively) was higher than that in healthy group (11.0 and 0 % respectively). Notably, neither group was positive for antibodies against double-stranded DNA or mitochondria. In conclusion, our results provide evidence for a polyclonal activity in Hashimoto's thyroiditis, an organ-specific autoimmune disease, associated with an altered prolactin-adrenocortical status. Such information should initiate longitudinal studies to clarify the exact time sequence of these events related to the disease's activity.     

Plasma 7B2 (a novel pituitary protein) immunoreactivity concentrations in patients with various endocrine disorders

We have measured plasma 7B2 (a novel pituitary protein)-immunoreactivity (IR) concentrations in patients with various endocrine disorders. Mean (+/- SEM) basal plasma 7B2-IR concentrations (ng/L) in patients with acromegaly (81 +/- 14.6), Cushing's disease (57.2 +/- 8.5), prolactinoma (71.4 +/- 9.5), panhypopituitarism (50.6 +/- 7.6), isolated ACTH deficiency (47.9 +/- 11.6), hyperthyroidism (57.9 +/- 6.7) and hypothyroidism (60.8 +/- 9.4) were on the same levels as those in age-matched normal subjects. However, basal plasma 7B2-IR concentrations were increased to more than 100 ng/L in 5 out of 25 patients with acromegaly (20%). Mean basal plasma 7B2-IR concentrations in patients with medullary carcinoma of the thyroid and pheochromocytoma were 293 +/- 38.1 ng/L (range: 225.7-357.4 ng/L, n = 3) and 221 +/- 82.8 ng/L (range: 48.5-527.8 ng/L, n = 5), respectively, and significantly higher than those in age-matched normal subjects (P less than 0.001). These results suggest that plasma 7B2-IR may have some diagnostic value for acromegaly and may be useful as a marker for medullary carcinoma of the thyroid and pheochromocytoma.     

Absence of suppressive effect of somatostatin on prolactin levels in patients with hyperprolactinemia

The effect of somatostatin (SRIF: 10 micrograms/min during 120 min) on serum prolactin (PRL) levels was studied in eleven patients with hyperprolactinemia of varying causes: 2 patients with acromegaly; 2 with primary hypothyroidism; 4 with prolactinoma and 3 with drug (sulpiride) induced hyperprolactinemia. During SRIF infusion, no significant change in PRL levels was observed in any of the 4 groups studied except in one female patient with a prolactinoma. The biological activity of SRIF was demonstrated by the significant inhibition (P less than 0.05) of insulin levels seen in all 11 patients (52% fall in relation to basal) without simultaneous modification of glycemia. These data suggest that SRIF does not decrease PRL secretion in most patients with hyperprolactinemia.     

Radioimmunoassay for estimation of thyroglobulin in human serum.

A specific double antibody radioimmunoassay has been develop for the measurement of thyroglobulin in human serum. Human thyroglobulin was purified by combined DEAE-cellulose and affinity chromatography using Sepharose 4B-bound Concanavalin A. Sensitivity of test serum was 10 ng/ml. Thyroglobulin was not detectable in half of normal subjects, and half showed values between 10 and 180 ng/ml. In the patients with simple goiter and secondary hypothyroidism, serum thyroglobulin was usually in the normal range. In Hashimoto's thyroiditis, many sera having precipitating antibodies or high hemagglutination antibodies for thyroglobulin showed a high thyroglobulin concentration in serum probably due to a false positive reaction. In hyperthyroidism, an increased thyroglobulin level was observed in 64% of patients. However, there was no correlation between serum thyroglobulin and thyroxine levels in untreated hyperthyroidism. Serum thyroglobulin was increased significantly in some cases for several weeks after isotope therapy for the hyperthyroidism.     

Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults

OBJECTIVE: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). METHODS: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. RESULTS: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. CONCLUSION: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.     

Growth hormone-releasing factor (GRF) stimulation test in the diagnosis of pituitary adenomas

The studies aimed at evaluation of pituitary reserve of growth hormone following stimulation with GRF have been carried out in a group of 33 patients (11 women and 22 men, of age between 25 and 62 years) with pituitary tumors. The studied material included cases with pituitary adenoma characterized by excessive secretion of growth hormone (somatotropinoma), prolactin (prolactinoma) or alpha subunits of glycoprotein hormones (alphoma), and those with hormonally inactive adenoma. The GRF stimulation tests were carried out in hospitalized patients after overnight fast between 8.00 and 10.00 a.m. Blood samples for hormonal determinations were taken before the test, and after 15, 30, 60, 90 and 120 minutes following intravenous administration of 100 micrograms of GRF 1-29. Besides growth hormone, also the blood serum concentrations of other pituitary hormones were determined in the patients studied, both in the basal state and during the dynamic tests. In patients with acromegaly the results of the determinations of growth hormone following stimulation with GRF showed considerable individual variability. In 5 cases there was an increase in blood serum growth hormone concentration. No response to GRF was noted in the remaining 8 cases. In adenoma cases of prolactinoma type, growth hormone concentration began to rise already at the 15-th minute of the test in most cases. In three cases of prolactinoma associated with acromegaly no response to GRF was observed. The cases of alphoma-type adenoma were usually characterized by the secretion of pituitary hormones other than growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)     

A simple semiquantitative radiometric measurement of antithyroglobulin antibodies in human serum. Comparison with hemagglutination method

A simple solid-phase radiometric assay for the measurement of thyroglobulin autoantibodies (TgRA) was developed and evaluated. The assay is semiquantitative, and the results were expressed as a ratio between sample versus negative control (normal human serum). In 59 normal subjects, the mean ratio was 0.93 +/- (SD) 0.34. Thyroglobulin antibodies by radiometric assay, by hemagglutination (TgHA), as well as microsomal antibodies by hemagglutination (MCHA) were measured in 41 patients with a histopathologic diagnosis of Hashimoto's thyroiditis (n = 22), adenomatous goiter (n = 10), carcinoma (n = 5), adenoma (n = 4), and in 59 patients without histopathologic diagnosis of thyroid disease. In patients with Hashimoto's thyroiditis, TgRA, TgHA, and MCHA were positive in 54, 31, and 81% of patients, respectively. 1 patient had positive TgRA with negative MCHA levels, and 2 had negative antibody titers by all methods. Thyrotropin-stimulating hormone levels were elevated (greater than 10 microU/ml) in 17 of these patients. Our results suggest that although the TgRA method is more sensitive than TgHA for detecting thyroglobulin antibodies, its diagnostic sensitivity is not equal to that of MCHA.     

Diagnostic Value of Thyrotropin-Releasing-Hormone Stimulation in Patients With Pituitary Tumor

Plasma prolactin response to thyrotropin-releasing-hormone (TRH) stimulation was diminished in 30 patients with prolactinomas and 9 patients with acromegaly who had normal serum prolactin levels. There was no overlap of prolactin responses when compared with 32 control patients. Responses of ten patients with adrenocorticotropin (ACTH)-secreting pituitary tumors were similar to those of controls. Plasma growth hormone concentrations after TRH stimulation changed significantly in 28% of normal control and 20%, 25% and 50% of patients with prolactin-, growth hormone- and ACTH-secreting pituitary tumors, respectively. Our data suggest that the blunted TRH-induced rise in plasma prolactin levels in patients with prolactinomas and those with acromegaly may be related to humoral factor(s) affecting TRH receptor or postreceptor function. Growth hormone responses to TRH are nonspecific and should not be considered a marker for active acromegaly.     

Production of anti-human thyroglobulin and anti-thyroid hormone antibodies in rabbits immunized with human thyroglobulin

Two rabbits (TG-1, TG-2) were immunized with human thyroglobulin (HTg) and bled serially. Antisera were obtained at different times after the first immunization and kept separately and studied. In both rabbits production of anti-HTg, and anti-thyroid hormone antibodies such as anti-thyroxine (T4) and anti-triiodothyronine (T3) antibodies was observed. Binding parameters of anti-HTg antibodies with HTg, T4, and T3 were calculated in two selected antisera (70-day and 249-day). The Scatchard's plots of these antibodies were all curve-linear and were analyzed in two components: one, higher binding constant (Ka1) and smaller binding capacity (Cap1) and the other, lower binding constant (Ka2) and larger binding capacity (Cap2). Ka1 values of anti-HTg, anti-T4, and anti-T3 antibodies in sera from TG-1 obtained from 70-day and 249-day bleeding were 1.1 X 10(10) M-1, 6.0 X 10(9) M-1. 7.9 X 10(8) M-1 and 1.7 X 10(10) M-1, 6.5 X 10(9) M-1, 1.0 X 10(9) M-1, respectively. Those from TG-2 were 1.7 X 10(10) M-1, 1.8 X 10(9) M-1, 6.4 X 10(8) M-1 and 2.0 X 10(10) M-1, 3.1 X 10(9) M-1, 1.6 X 10(9) M-1, respectively. The significance of the production of anti-HTg and anti-thyroid hormone antibodies in rabbits immunized with HTg in relation to the antigenic structure of HTg molecule was discussed.     

Increased micronucleus,nucleoplasmic bridge,nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma

Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically signi?cant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2’-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.     

Toxoplasma gondii infection and schizophrenia: a case control study in a low Toxoplasma seroprevalence Mexican population

There are conflicting reports concerning the association of Toxoplasma gondii infection and schizophrenia in humans. Therefore, we determined such association in a Mexican population of Mestizo ethnicity. Through a case-control study design, 50 schizophrenic patients and 150 control subjects matched by gender, age, residence place, and ethnicity were examined with enzyme-linked immunoassays for the presence and levels of T. gondii IgG antibodies and for the presence of T. gondii IgM antibodies. Schizophrenic patients attended a public psychiatric hospital in Durango City, Mexico, and the control group consisted of individuals of the general population of the same city. Socio-demographic, clinical and behavioral characteristics from the study subjects were also obtained. Both the seroprevalence and the level of T.gondii IgG antibodies were higher in schizophrenic patients (10/50; 20%) than in control subjects (8/150; 5.3%) (OR=4.44; 95% CI: 1.49-13.37; P=0.003). The IgG T. gondii levels higher than 150 IU/ml were more frequently observed in patients than in controls (10% versus 2%, respectively; P=0.02). One (50%) of the two patients with recently diagnosed schizophrenia and none of the controls had T. gondii IgM antibodies (P=0.01). T. gondii seropositivity was significantly higher in patients with a history of cleaning cat excrement (P=0.005), and suffering from simple schizophrenia (ICD-10 classification: F20.6) (P=0.03) than patients without these characteristics. Toxoplasma seroprevalence was also significantly higher in patients with simple schizophrenia (F20.6) than in those with paranoid schizophrenia (F20.0) (P=0.02). This study provides elements to clarify the controversial information on the association of T. gondii infection and schizophrenia.     

Plasma aldosterone response to metoclopramide is unmodified by hyperprolactinemia

It has been previously demonstrated that patients with hyperprolactinemia have impaired PRL response to dopaminergic blockade and increased TSH response. Since inhibitory dopaminergic modulation of aldosterone is well established, we have examined whether prolactinoma patients have an altered aldosterone response to dopaminergic blockade. To investigate this possibility we compared the plasma PRL, TSH and aldosterone responses to the dopamine (DA) antagonist metoclopramide (MCP; 10 mg i.v.) in 10 women with prolactinomas and 7 healthy female controls. Basal PRL levels in prolactinoma patients were elevated and showed a blunted rise following MCP. Although basal TSH levels were similar in the 2 groups of subjects, they significantly increased (p = 0.017) in prolactinoma patients while in contrast they did not significantly change in control subjects. Basal supine plasma aldosterone was similar in patients with prolactinomas (0.23 +/- 0.03 nmol/l) and in healthy subjects (0.25 +/- 0.04 nmol/l) and the increased aldosterone concentrations from 15 to 120 min following MCP were not significantly different in prolactinoma patients and in control subjects. It is concluded that in patients with prolactinomas, the alteration in the dopaminergic regulation is specifically related to the lactotroph.     

Effect of opiates on growth hormone secretion in acromegaly.

Morphine at doses of 5 mg and 10 mg does not stimulate growth hormone (GH) secretion in normal subjects, and its effect on GH secretion in acromegaly is not widely documented. We investigated the effect of 15 mg intravenous morphine on growth hormone in patients with active acromegaly compared to normal subjects (7 acromegalics and 5 controls). Their mean (+/- SEM) age was 30.5 +/- 7.6 years and 29.5 +/- 0.5 years, respectively. Basal and peak response of growth hormone after morphine was measured with simultaneous assay of cortisol to exclude the effect of stress. Mean (+/- SEM) basal growth hormone was 103.16 +/- 28.04 ng/ml in acromegalics compared to 4.51 +/- 1.43 ng/ml in controls. Morphine caused an elevation of growth hormone in both acromegalics and normal subjects (p < 0.05). However, the Delta (peak minus basal) response of growth hormone was comparable between the two groups. A concurrent fall in cortisol was noted after morphine in both the groups, excluding the effect of stress on growth hormone. We conclude that higher doses (15 mg) of morphine are required to stimulate GH secretion in normal subjects, and that opioids exert a positive modulating effect on growth hormone secretion in patients with active acromegaly suggesting partial autonomy of the pituitary tumor.