Maximal Increment Research Articles

Abnormal renin short feedback loop in essential hypertension is reversible with converting enzyme inhibition.

The suppression of renin release by angiotensin II (AII) (the so-called short feedback loop) is blunted in essential hypertension. To determine whether this abnormality is reversible, renin release was assessed in sodium-restricted essential hypertensives and normal controls: (a) during the administration of captopril for varying intervals and (b) following the infusion of graded doses of AII (0.3-3 ng/kg per min) before and after plasma levels of AII had been chronically reduced with captopril (25-50 mg every 6 h) for 70 h. In control subjects, the maximal increment above control in plasma renin activity (PRA) after a single dose of captopril (11.9+/-3 ng/ml per h) was significantly (P < 0.02) greater than in hypertensives (8.1+/-1.7 ng/ml per h) despite similar reductions in AII levels and significantly greater decrements in diastolic blood pressure in the hypertensives. When captopril was continued for 70 h, the PRA increments above base line in hypertensive subjects (11.4+/-2.9 ng/ml per h) rose to levels seen in the controls (11+/-2.6 ng/ml per h); there were no significant differences in the AII or diastolic blood pressure decrements between the two groups. Compared with normotensive subjects, AII failed to suppress renin release in hypertensive subjects despite significantly greater diastolic blood increments and comparable AII levels achieved at each AII dose. After captopril treatment, AII now produced significant declines in PRA in the hypertensives; moreover, comparing declines pre- and postcaptopril, greater PRA decrements were seen either at comparable rises in levels of AII or diastolic blood pressure. Finally, the suppression of PRA by AII postcaptopril in hypertensives was now indistinguishable from that seen in normal controls. Thus, the impaired regulation of renin by AII is reversible with prolonged captopril treatment, suggesting that this abnormality is not due to a fixed structural defect but to a reversible lesion.

Isoproterenol responsiveness and myocardial beta-adrenergic receptors in young and old rats.

To elucidate the association of beta-adrenergic receptors with decreased myocardial catecholamine responsiveness in aging, we investigated the chronotropic response to isoproterenol and myocardial beta-adrenergic receptors in Fisher 344 rats of 3, 12, and 24 months of age. Heart rate response to isoproterenol (50 mug/kg, subcutaneously) was greatest in 3-month-old animals, both in maximum heart rate achieved and increment over baseline. Twelve-month-old animals had significantly lower maximal hear rates (p less than .025) and increment over pretreatment, basal minus isoproterenol-stimulated heart rates (p less than .005), when compared with 3-month-old animals. Twenty-four-month-old rats were less responsive than either 12- or 3-month-old animals both with respect to maximal rates (p less than .05, .005, respectively) and increments (p less than .005, .001, respectively). There were no changes in the density or affinity of myocardial, lymphocytic, or pulmonary beta-adrenergic receptors as measured by [3H]-dihydroalprenolol binding in the three age groups investigated. Our data are consistent with the concept that the beta-adrenergic stimulatory pathway is impaired with age. The demonstration of unaltered myocardial beta-adrenergic receptor number and affinity with age suggests that myocardial catecholamine responsiveness is impaired at a level other than the beta-adrenergic receptor site.

Diabetes Mellitus Following Pentamidine-induced Hypoglycemia in Humans

Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postabsorptive state. 28 +/- 1 microunits/ml (blood glucose 41 +/- 4 mg/dl) and 86 +/- 5 microunits/ml (blood glucose 15 +/- 5 mg/dl) vs. 15 +/- 3 microunits/ml in 10 control subjects and 55 +/- 3 microunits/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 microunits/ml vs. + 40 microunits/ml in control group and +77 microunits/ml in the insulinoma group), by i.v. arginine (maximal increment + 10 and +28 microunits/ml, respectively, vs. +55 in the controls and +90 microunits/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 microunits/ml, respectively) vs. +40 microunits/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10(-10) M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.

Effect of sulpiride on plasma TSH secretion in various hypothalamo-pituitary disorders (author's transl)

It is commonly accepted that hypothalamic dopamine has an inhibitory role not only on prolactin but also on TSH secretion. To study the hypothalamic dopaminergic participation in TSH secretion in various hypothalamo-pituitary disorders, we examined the effect of sulpiride, a dopamine antagonist. Using a commercially available human TSH radioimmunoassay (RIA) kit and improving it, we developed a high sensitivity RIA for human TSH (assay sensitivity: 0.15 micro Units/ml, 50% B/B0 values: 3.47 micro Units/ml). In 18 normal controls, plasma TSH increased significantly after intramuscular injection of sulpiride of 1.01 +/- 0.17 micro Units/ml (Mean +/- SEM). In 61 patients with pituitary adenoma, plasma TSH responses to sulpiride were significantly greater than those of normal controls, and the mean maximal increments were as follows: 1.65 +/- 0.24 micro Units/ml in acromegaly (n = 21), 2.63+/- 0.55 micro Units/ml in non-functioning pituitary adenoma (n = 23), and 4.49 +/- 0.70 micro Units/ml in prolactin producing pituitary adenoma (n = 17), respectively. The maximal TSH responses to sulpiride in prolactin-producing pituitary adenoma were significantly greater than those in non-functioning pituitary adenoma (p less than 0.05) and those in acromegalic patients (p less than 0.001). On the other hand, we could observe no TSH responses to sulpiride in 9 cases of hypothalamic tumor with hyperprolactinemia. These results suggest that the dopaminergic inhibitory influence on TSH secretion is increased in patients with pituitary adenoma, and that it is especially dominant in patients with prolactin producing pituitary adenoma. It is concluded that hypothalamic dopaminergic tone can be evaluated indirectly by the sulpiride test, and that the test is useful in the differential diagnosis of hypothalamo-pituitary disorders.

Stimulation of 1,25-dihydroxyvitamin D production by parathyroid hormone and dibutyryl 3',5'-cyclic AMP in normal subjects,hypoparathyroidism and pseudohypoparathyroidism.

Parathyroid extract (PTE) or synthetic 1-34 human parathyroid hormone (1-34 hPTH) was injected intravenously as a bolus in 4 normal subjects, 4 patients with PTH deficient hypoparathyroidism (HP) and 3 patients with pseudohypoparathyroidism (PHP). In normal subjects and HP, plasma 1,25(OH)2D was markedly increased at 6 hr and reached the peak at 12 or 14 hr after administration of 200 units of PTE or 20 to 30 micrograms of 1-34hPTH. On the other hand, 500 units of PTE or 20 micrograms of 1-34hPTH failed to increase plasma 1,25(OH)2D in PHP. However, 2.5 mg/kg of dibutyryl cAMP remarkably increased plasma 1,25(OH)2D in a patient with PHP. Maximal increments of plasma 1,25(OH)2D in 3 patients with HP(21.7 +/- 5.6 pg/ml, mean +/- S.D.) were nearly as high as in normal subjects (20.6 +/- 7.0 pg/ml), whereas those in 3 patients with PHP (2.3 +/- 2.3 pg/ml) were distinctly lower than in normal subjects or HP. It is suggested that 1,25(OH)2D production by PTH is intact in HP, but is impaired in PHP mainly due to a defect in the activation of adenylate cyclase system.

Diagnosis of hypogonadotrophism versus delayed puberty in the male at pubertal age

This differentation often appears impossible at pubertal age. In groups of boys the conditions differ in plasma testosterone response to HCG and LH response to GnRH. However, in clinically unclear individual cases the tests often fail too. We have followed 32 boys until the diagnosis of hypogonadotrophism was clinically certain. All had been given a GnRH test (3.5 μg/kg up to the maximum of 100 μg GnRH iv) and some an HCG test (5000 IU/m2 im on days 1, 3, 8 and 10, with determination of serum testosterone on days 1 and 15). We have compared their results with the results of 68 normal boys at similar, usually markedly delayed development. Every primary test parameter showed an overlap between the two groups. Best in discrimination were the logarithms of stimulated testosterone level (lnTs) and maximal increment in LH level (lnΔ LHmax). The lower limit of 90% confidence range for lnTs in the reference series detected 6/8 of the hypogonadotrophic against none of the reference boys. The same limit for lnΔLHmax detected 64% of the hypogonadotrophic boys in 47 tests against 4% of the reference boys. The product of these two parameters (lnTs × lnΔLHmax) appears superior. Data being so far available for 8 hypogonadotrophic and 17 reference boys, these groups are completely separated by the product, and with a wide margin. Further data are being collected to allow a reliable evaluation of this new diagnostic parameter.

The effect of prostaglandin E2 and ADH on diffusional water permeability in collecting duct of an isolated rat papilla.

The effect of prostaglandin on diffusional water permeability has been studied in collecting ducts in an isolated rat papilla. PGE2 increased water permeability. The effect was significant at a concentration of 10(-8) mol 1(-1) and was maximal with a concentration of 10(-6) mol 1(-1). The maximal increment of 0.94 +/- 0.10 (SEM) micron s-1 was approximately half that produced by maximal stimulation with antidiuretic hormone (2.18 +/- 0.12 micron s-1). A concentration of 10(-8) mol 1(-1) produced an increase in basal water permeability and 24 mu unit ml-1 ADH, which without PGE2 present gave a similar increase, had no incremental effect. ADH 100 mu unit ml-1 increased permeability to a value similar to that observed in the absence of PGE2. Thus PGE2 and ADH both increase water permeability but the increments are not additive. Indomethacin in a concentration that inhibited prostaglandin production altered the response of the collecting duct to ADH. The dose response curve was shifted to the left and the maximal increase in water permeability and the lowest dose at which a response occurred took place at concentrations less than 1/2 those required in its absence. Prostaglandins influence the action of ADH and it is likely that in life they regulate and modulate the change in water permeability induced by anti-diuretic hormone.

Regulation of prolactin and thyrotrophin secretion during human pregnancy: effect of sulpiride and TRH administration.

Abstract. The regulation of prolactin (Prl) and thyrotrophin (TSH) secretions during early human gestation was studied in 30 healthy women. Twelve women were treated with oral sulpiride, 150 mg daily for two weeks, and the Prl and TSH responses to 220 μg of iv thyrotrophin-releasing hormone (TRH) were measured before and at the end of sulpiride administration. Eight women were given 200 mg of sulpiride im, and 4 of them received 200 μg of TRH 30 min later. In 4 women the order of the TRH and sulpiride injections was reversed. Six women were studied as controls. Oral sulpiride treatment induced a significant Prl elevation from 14.6 ± 1.8 μg/l (mean ± sem) to 83.0 ± 4.0 μg/l, whereas the mean TSH levels did not change. Before sulpiride intake, TRH caused a mean maximal increment of 42.9 ± 4.7 μg/l in the Prl levels and an increment of 5.6 ± 0.9 IU/l in the TSH levels. During sulpiride administration, TRH caused a mean maximal increment of 16.5 ± 4.7 μg/l in the Prl levels and 3.5 ± 0.6 IU/l in the TSH levels. Both responses were significantly smaller (P &lt; 0.001) during the sulpiride treatment than before. Intramuscular injection of sulpiride raised the mean Prl concentration by 282 ± 32 μg/l (P &lt; 0.001) and the mean TSH concentration by 0.5 ± 0.1 IU/l (P &lt; 0.05). The Prl elevation was 502 ± 109 μg/l when sulpiride was injected after TRH. A preceding im sulpiride injection caused no changes in Prl and TSH responses to TRH. These results show that in addition to Prl also TSH secretion is partially controlled by the dopaminergic system during early human pregnancy.

Nicotinic acid test in the diagnosis of Gilbert's syndrome: correlation with bilirubin clearance.

A provocation test with nicotinic acid (50 mg intravenously) was performed in 13 patients with Gilbert's syndrome and seven healthy volunteers to investigate the diagnostic value of several test parameters and to correlate them with the bilirubin clearance. The maximal increment of unconjugated serum bilirubin, the retention at four hours, and the area under the bilirubin concentration time curve. (AUC) were measured. Significant differences between patients and controls were found with regard to the AUC (7.95 +/- SD, 3.29 mmol/min/l vs. 3.08 +/- 0.57; P less than 0.001), the increment of unconjugated bilirubin (24.1 +/- 7.1 mumol/l vs. 10.2 +/- 3.2; P less than 0.001) and the retention (77.7 +/- 8.9% vs. 45.8 +/- 27.4%; P less than 0.02). Of those, the AUC discriminated best between patients and controls. Five patients with Gilbert's syndrome had normal serum bilirubin concentrations (less than 17.1 mumol/l = 1 mg%) at the time of the study, but abnormal AUC and bilirubin increment. A significant correlation was found between the bilirubin clearance and the retention (r = -0.96; P less than 0.001) as well as the AUC (r = -0.82; P less than 0.05) but not with the bilirubin increment. This simple test may be used to assess the disturbance of bilirubin clearance in Gilbert's syndrome.

Failure of dopaminergic blockade to affect prolactin, growth hormone, and cortisol responses to insulin-induced hypoglycemia in schizophrenics.

The PRL, GH, and cortisol responses to insulin tolerance tests (ITTs) were evaluated in 12 medically healthy schizophrenic patients during a drug-free period and after 1 and 6 weeks of treatment with penfluridol, a potent, long acting, dopamine-blocking neuroleptic. Hypoglycemic responses were the same before and during penfluridol therapy. Although resting PRL levels were evaluated during initial penfluridol therapy (week 1), hypoglycemia provoked a further substantial PRL increment, not significantly different in magnitude from that induced by hypoglycemia during the drug-free period. However, there was a 54% reduction (P less than 0.05) in the increase in the area under the PRL curve during week 6 compared to the drug-free period. Regarding GH and cortisol, resting levels, areas under the curve, and maximal increments after ITT were essentially the same during weeks 1 and 6 of penfluridol treatment as in the drug-free period. The failure of 1 week of dopaminergic blockade to significantly alter the hormonal (PRL, GH, and cortisol) responses to ITT in the group as a whole suggests that dopamine-blocking mechanisms play little role in mediating these responses, at least in schizophrenic patients.

Regulation of TSH secretion and thyroid function in Cushing's disease.

In 15 untreated patients with Cushing's disease the regulation of TSH secretion and thyroid function was evaluated. The maximal increment of plasma TSH to TRH was 3.8 +/- 2.2 vs 8.7 +/- 2.9 muU/ml (patients with Cushing's disease vs controls; mean +/- SD; P less than 0.001). Free thyroxine-index was 21.8 +/- 5.2 vs 27.7 +/- 5.0 (P less than 0.001). Plasma T3 1.45 +/- 0.24 vs 1.96 +/- 0.32 nmol/l (P less than 0.001) and reverse T3 0.22 +/- 0.05 vs 0.20 +/- 0.08 nmol/l (N.S.). The maximal TSH increase in response to TRH was inversely correlated with plasma cortisol (P less than 0.05). The maximal increment of TSH to TRH and plasma T4, free T4 index and T3 are reduced in patients with Cushing's disease due to an impaired thyrotroph function. Plasma reverse T3, however, is normal which may be due to a simultaneous decrease in production and degradation.

The determination of glycosylated hemoglobins in rats using high pressure liquid chromatography

Glycosylated hemoglobins (GHb) or fast hemoglobins (FH) are minor components of hemoglobin that so far have been quantified in men, monkeys, and mice, and they are elevated in diabetic subjects of all these species. Since the rat is a useful model for experimental diabetic studies, hemolysates from streptozotocin-induced diabetic rats were analyzed for FH fractions using a high pressure liquid chromatography method. In a long-term study (3 mo), the maximal increment of the FH fractions was achieved after 5 wk of diabetes (from 5.67% ± 0.41% SD to 10.80% ± 0.74%) supporting the notion that the biosynthesis of these compounds occurs continuously during the lifespan of the red cell. In a short-term study. however, an elevation of the FH by 11% after 2 days and by 26% after 6 days of diabetes was noticed suggesting that a rapid increase of the FH may occur in relation to rapid changes of the glucose level.

13 GONADOTROPHIN RESPONSE TO Gn-RH IN PATIENTS TREATED WITH CYCLOPHOSPHAMIDE

The gonadotrophin response to Gn-RH was studied in 18 males with nephrotic syndrome treated with cyclophosphamide in a total dosis ranging from 2 to 94gm. Evaluation was performed from 6 months to 10 years after completion of therapy. Patients were divided in 3 groups: a) 8 prepubertal (6 to 9y) b) 8 pubertal (11 to 17y) and c) 2 adults (20y). LH and FSH were measured by RIA and results given in ng/ml LER 907. Normal values in our laboratory are (X ± SD) basal (B) and maximal increment (MI): B and and post Gn-RH gonadotrophin values did not differ significantly from controls. However, elevated FSH values were found in cne patient of group a, who received the highest cyclophosphamide dosage of this group. It is concluded that at the time of the study in 17/18 patients there was no testicular damage capable to produce a gonadotrophin elevation.

Direct stimulatory effect of histamine on aldosterone secretion of the perfused dog adrenal gland.

The left adrenal gland of the hypophysectomized-nephrectomized dog was perfused in situ with the blood from the femoral artery of the hypophysectomized-nephrectomized donor dog. After infusion of histamine (0.1 mg/min for 5 min) into the arterial inflow circuit, the rates of secretion of aldosterone, corticosterone and cortisol (ng/100 mg adrenal wt. each min) increased from the basal level of 0.66+/-0.21 (mean+/-S.E.M.) to 2.24+/-0.45 at 10 min, from 4+/-1 to 20+/-4 at 5 min and from 19+/-5 to 64+/-15 at 5 min, respectively. The maximal increments above the basal value after the infusion of histamine in the secretory rates of aldosterone, corticosterone and cortisol were 51, 16, and 13% that of the respective steroid after the infusion of ACTH (20mIU/min for 5 min). The results indicate that histamine has a direct stimulatory effect on the secretion of aldosterone by the adrenal gland as well as on that of corticosterone and cortisol.

Role of the renin-angiotensin system in enhancing the aldosterone response to adenocorticotropin during acute sodium depletion in normal subjects.

The role of the renin-angiotensin system in enhancing aldosterone responsiveness to ACTH during acute sodium depletion was studied in 14 healthy medical students. Acute sodium depletion was achieved by oral treatment with 80 mg furosemide and 200 mg SQ 14,225 for 1 day. The im administration of 250 micrograms alpha ACTH-(1-24) or vehicle was performed at 0800-0900 h both on the day after ad libitum diet (control) and 1 h after the oral administration of 50 mg SQ 14,225 on the day after acute sodium depletion. Treatments with furosemide and SQ 14,225 before both ACTH and vehicle administration induced a reproducible sodium depletion, accompanied by a marked increase in PRA and no significant increase in plasma aldosterone. The administration of ACTH, but not of vehicle, produced significant increases in plasma aldosterone in both control and acute sodium-depleted subjects. However, the ACTH-induced increases in plasma aldosterone and their maximal net and percent increments during acute sodium depletion were significantly greater than control values. It is concluded that angiotensin II does not play an important role in enhancing the aldosterone-stimulating activity of ACTH during acute sodium depletion and that sodium depletion per se may be responsible for this enhancement.

Bromocriptine suppresses the thyrotrophin response to thyrotrophin releasing hormone during human pregnancy.

Thyrotrophin (TSH) responses to 200 microgram of intravenous thyrotrophin releasing hormone (TRH) were measured in fifteen healthy women in normal early pregnancy before and at the end of a bromocriptine treatment of 5.0-7.5 mg daily for 1-2 weeks. Bromocriptine did not change the basal levels of TSH, triiodothyronine (T3) and thyroxine (T4) during pregnancy. Before the start of bromocriptine, TRH caused a significant TSH elevation from 12.8 +/- 0.5 muu/ml (mean +/- SE) to 21.2 +/- 1.9 muu/ml after 20 min. During bromocriptine intake, TRH caused a TSH elevation from 11.9 +/- 0.4 muu/ml to only 15.5 +/- 1.1 muu/ml which is significantly less (P less than 0.001) than before bromocriptine. Similarly, the mean maximal TSH increment of 8.4 +/- 1.5 muu/ml before bromocriptine was greater (P less than 0.001) than that of 3.8 +/- 60 muu/ml during bromocriptine intake. When women were retested with TRH before and during bromocriptine after legal abortion, bromocriptine did not change the basal levels of TSH, T3 and T4 or the TSH response to TRH. Therefore, the TSH inhibition caused by bromocriptine is specifically related to the pregnancy itself, but the mechanism for this inhibition remains unknown.

Comparison of glucagon responses to 2-deoxy-D-glucose and hypoglycemia in man.

2-Deoxy-D-glucose (2DG), by competitive inhibition of glucose utilization, produces a state of intracellular glucopenia with resultant activation of both the sympathetic and parasympathetic branches of the autonomic nervous system. We have investigated the relationship between the activation of the autonomic nervous system caused by this drug and glucagon secretion. Subjects experienced symptoms identical to those observed during true hypoglycemia and demonstrated a marked rise in both gastric acid secretion and urinary epinephrine excretion. Mean immunoreactive glucagon (IRG) levels rose only slightly post-2DG (maximal mean increment, 18 pg/ml). Insulin-induced hypoglycemia, although eliciting a similar increase in urinary epinephrine excretion, was followed by a severalfold increase in IRG. Thus, although hypoglycemia and 2DG induced similar discharge of the autonomic nervous system, the glucagon response to hypoglycemia was much greater. These observations provide strong evidence that marked increases in sympathetic and parasympathetic discharge in man are weak alpha-cell stimuli and further support the hypothesis that the rise in IRG that occurs during hypoglycemia is not mediated primarily via the autonomic nervous system.

Effects of gestational diabetes on diurnal profiles of plasma glucose, lipids, and individual amino acids.

To assess the effects of gestational diabetes mellitus (GDM) on intermediary metabolism in late pregnancy, circulating levels of glucose, FFA, triglycerides, cholesterol, and individual amino acids were monitored for 24 h while subjects received a liquid formula diet (containing 2110 cal and 275 g carbohydrate) in three equal feedings at 0800, 1300, and 1800. Attempts were made to distinguish between varying degrees of severity of gestational diabetes by subdividing the population into those with fasting plasma glucose within the normal range for pregnancy, i.e., below 105 mg/dl (GDM &amp;lt; 105), and those with fasting plasma glucose of 105 mg/dl or greater (GDM ≥ 105). Both groups were compared with pregnant women with normal carbohydrate metabolism (NM). The diurnal profiles indicated that premeal, postprandial averages, and integrated 24-h values for plasma glucose were consistently higher in GDM ≥ 105 than in GDM &amp;lt; 105; both GDM groups uniformly exceeded the values in NM. Plasma FFA tended to be higher in all GDM, with maximal increments occurring in the early hours before breakfast and assuming greatest significance in GDM ≥ 105. The elevations in circulating cholesterol that occur in pregnancy were not significantly different at any time point in NM, GDM &amp;lt; 105, and GDM ≥ 105. However, the increases in plasma triglycerides were greater in GDM &amp;lt; 105 and GDM ≥ 105 than in NM and most marked in GDM ≥ 105. Diurnal profiles for a number of individual amino acids (phenylalanine, tyrosine, alanine, serine, proline) were not affected by gestational diabetes. However, certain other amino acids, particularly the branched chain (leucine, isoleucine, valine), tended to be elevated in subjects with GDM and to the most significant extent in GDM ≥ 105. Although the GDM subjects tended to be heavier than the NM, the progressively more pronounced metabolic abnormalities in GDM ≥ 105 than in GDM &amp;lt; 105 would suggest that relative insulinopenia rather than obesity contributed to the differences. Our findings indicate that gestational diabetes is attended by disturbances of varying degrees in all major classes of insulin-dependent foodstuffs and must be viewed as a disorder of multiple fuels.

Does bromocriptine block thyrotropin-releasing hormone-induced prolactin release during pregnancy?

PRL responses to 200 microgram of iv TRH were measured in 16 healthy women with normal early pregnancy before and at the endo of bromocriptine treatment of 5.0--7.5 mg daily for 1--2 weeks. Before the start of bromocriptine, TRH caused a PRL elevation from 19.1 +/- 2.2 to 95.2 +/- 12.6 ng/ml (mean +/- SE) after 20 min, with a mean maximal PRL increment of 71.7 +/- 11.6 ng/ml. Bromocriptine suppressed basal plasma PRL level to 3.6 +/- 0.8 ng/ml (P less than 0.001). TRH then caused a PRL rise to 18.8 +/- 1.8 ng/ml at 20 min, with a mean maximal PRL increment of 15.7 +/- 1.8 ng/ml. The absolute PRL response was significantly smaller (P less than 0.001) during bromocriptine intake than before, whereas the mean percent increments in PRL levels after TRH administration were similar in the presence and absence of bromocriptine. Fifteen of these women were restudied with TRH stimulation 4--6 weeks after legal abortion, and the PRL responses to TRH were normal. When 7 of these women were once again treated with bromocriptine and retested with TRH, no absolute or relative PRL response to TRH emerged. These results release differs between the pregnant and nonpregnant states.

Thyroid function tests in patients on regular hemodialysis.

Serum thyroxine (T₄), triiodothyronine (T₃), the T₃ resin uptake test (T₃RU) and TSH were measured in 85 clinically euthyroid patients on regular haemodialysis; sera were collected immediately before dialysis. 32% of patients had goitres. Serum T₃ was below the normal range in 34% and T₄ in 39%; the T₃RU was in the high normal range in most. Serum TSH was slightly elevated in 13 patients. In 20 patients dialysed for 3 months or less the serum T₄ was normal in 18 and the free thyroxine index (FTI) was normal in every case; mean T₄ and FTI values were significantly lower in patients dialysed for more than 3 months. 16 patients were studied prospectively on two occasions 14 months apart; those initially dialysed for less than 1 year showed a significant fall in mean T₄ and FTI values after a further 14 months of dialysis, while levels were unchanged in those dialysed initially for more than a year. Thyroid hormone levels were measured before and immediately after a single dialysis in 57 patients. Dialysis caused significant acute elevations of T₃, T₄, and FTI, but had no consistent effect on TSH. The TSH and prolactin responses to TRH were investigated in 18 male patients: the mean maximal TSH increment was significantly lower than in controls and peak responses were subnormal in 5 patients. Basal serum prolactin levels were elevated but peak responses were normal. It is concluded that, in patients on regular haemodialysis: (1) goitre may be frequent; (2) <i>in vitro</i> thyroid function tests were often subnormal just before a period of dialysis, but were usually normal immediately after the dialysis; (3) serum T₄ levels fall rapidly in the first year of dialysis; (4) the pituitary responsiveness to low serum thyroid hormone levels and to exogenous TRH is often abnormal in dialysed patients, although they appear to be euthyroid.