重组人生长激素治疗对生长激素缺乏症患者甲状腺功能的影响

为探讨生长激素治疗对甲状腺功能的影响及其机制，给１９例特发性生长激素缺乏症患者每日皮下注射重组人生长激素（ｒｈＧＨ）Ｇｅｎｏｔｒｏｐｉｎ０．１ＩＵ／ｋｇ体重，治疗１年，观察治疗前后甲状腺功能及血促甲状腺激素（ＴＳＨ）对静脉推注促甲状腺素释放激素（ＴＲＨ）的反应。经Ｇｅｎｏｔｒｏｐｉｎ治疗后，患者血清Ｔ４及ＦＴ４水平较治疗前明显下降（Ｐ＜０．０１）；治疗半年后，血清ＦＴ３水平亦较治疗前下降（Ｐ＜０．０５）；而血清Ｔ３、３，３′，５′－三碘甲状腺原氨酸及ＴＳＨ水平无明显变化（０．２＜Ｐ＜０．３）。治疗１年后，８例患者血清ＦＴ４水平降至正常范围以下，依此将患者分为治疗后甲状腺功能正常组及降低组，结果证实甲状腺功能降低组在治疗前或治疗后ＴＳＨ对ＴＲＨ兴奋的反应均较甲状腺功能正常组高（Ｐ＜０．０５）。血清ＴＳＨ对ＴＲＨ的反应增强提示患者治疗前就已有潜在的ＴＲＨ缺乏，后者可能是ｒｈＧＨ治疗过程中ＦＴ４及Ｔ４水平下降的潜在基础。因此在ｒｈＧＨ治疗过程中需监测特发性生长激素缺乏症患者的甲状腺功能，以及时给予替代治疗。     

固真方对老年大鼠下丘脑—垂体—甲状腺轴和免疫功能的影响

研究发现，与青年组比较，老年大鼠血清游离甲状腺素Ｔ４（ＦＴ４）、游离甲状腺素Ｔ３（ＦＴ３）水平明显下降，而血清３，３′，５′三碘甲腺原氨酸（ｒＴ３）水平显著升高，血清促甲状腺释放激素（ＴＲＨ）、促甲状腺激素（ＴＳＨ）呈代偿性增高，下丘脑ＴＲＨ明显下降，血清胸腺因子活性和脾细胞白介素２（ＩＬ２）活性降低。固真方可明显提高老年大鼠下丘脑ＴＲＨ、垂体ＴＳＨ，血清ＦＴ４与ＦＴ３，降低老年血清增高的ＴＲＨ、ＴＳＨ、ｒＴ３，使老年大鼠血清胸腺因子和ＩＬ２活性增高。     

糖尿病血清甲状腺激素水平的变化及其临床意义

对糖尿病患１７１例、正常健康成人３０例，采用放射免疫地测定其甲状腺激素水平。结果 糖尿病患血清总Ｔ３（ＴＴ３）、总Ｔ４（ＴＴ４）、游离Ｔ３（ＦＴ３）、游离Ｔ４（ＦＴ４）水平平均显低于正常对照组（Ｐ值均〈０．０１），血清ＴＳＨ水平无明显变化，ｒＴ３，水平显升高，（Ｐ〈０．０５）。结论 糖尿病患血清ＴＨ水平下降，ｒＴ３升高，ＴＳＨ无变化对其甲状腺功能的评价具有重要意义。     

原发性肝癌FT3,FT4,TT3测定的临床意义

４０例原发性肝癌（ＰＨＣ）施行肝动脉栓塞前、后测定了ＦＴ３、ＦＴ４、ＴＴ３、ＴＴ４和ＴＳＨ水平。结果：ＴＡＥ前，ＦＴ３、ＦＴ４、ＴＴ３水平均低于正常人水平（Ｐ〈０．０１）。而ＴＴ４、ＴＳＨ两项有后无差异。本组结果还可见ＴＡＥ后ＦＴ３、ＦＴ４水平下降明显，与ＴＡＥ前差异有显著性意义（Ｐ〈０．０１）。而ＴＴ３与ＴＡＥ前的ＴＴ３相比，差异无显著差异（Ｐ〈０．０５）。另外，ＦＴ３、ＦＴ４值的降低与白蛋白呈     

结核性脑膜炎患者血清甲状腺激素水平的研究

本文采用放射免疫法检测３０例结核性脑膜炎患者血清甲状腺激素水平。结果表明：结脑患者血清ＴＴ４、ＴＴ３和Ｔ３ｒＴ３比值均较健康人为低（Ｐ＜０．０１），ｒＴ３和Ｔ３ＲＵ则增高（Ｐ＜０．０１），ＴＳＨ虽降低，但差异无显著性（Ｐ＞０．０５）ｍ，ＦＴ４Ｉ亦无显著性差异（Ｐ＞０．０５）。结果还提示，结脑患者甲状腺激素水平与病情有关。     

T_4甲亢及其处理

Ｔ４甲状腺功能亢进症（Ｔ４ｔｏｘｉｃｏｓｉｓ）或Ｔ４甲状腺中毒症，简称Ｔ４甲亢，是指甲状腺呈高功能状态，血清四碘甲状腺原氨酸（Ｔ４）单独升高，三碘甲状腺原氨酸（Ｔ３）正常或下降，多数促甲状腺激素（ＴＳＨ）受抑制，ＴＳＨ对促甲状腺激素释放激素（ＴＲＨ）...     

滤纸片法TRH兴奋试验在碘缺乏病中的应用

本文将血清法ＴＲＨ兴奋试验改为血滤纸片法，在新疆严重碘缺乏病区测定地方性克汀病２６例，其中粘肿型１０例、混合型１０例、神经型６例。滤纸片法ＴＲＨ兴奋试验结果：基础ＴＳＨ值（ＴＳＨ０）、ＴＳＨ峰值（注射ＴＲＨ３０，钟后的最高值ＴＳＨ３０，）、△ＴＳＨ绝对增值（ＴＳＨ３０，峰值减ＴＳＨ０）对不同类型的克汀病人分别为：粘肿型ＴＳＨ０１２０．２９±９３．７４μＩＵ／ｍｌ、ＴＳＨ３０，２２５．３０±１１２．０７μＩＵ／ｍｌ、△ＴＳＨ１０５．０１μＩＵ／ｍｌ；混合型ＴＳＨ０１０．５８±９．３６μＩＵ／ｍｌ、ＴＳＨ３０，６４．７８±３３．９８μＩＵ／ｍｌ；△ＴＳＨ５４．２０μＩＵ／ｍｌ；神经型ＴＳＨ０１．９８±０．６３μＩＵ／ｍｌ、ＴＳＨ３０，２６．７６±４９．９２μＩＵ／ｍｌ、△ＴＳＨ２４．７６μＩＵ／ｍｌ。三型克汀病间差异显著（Ｐ＜０．０１）．粘肿型克汀病ＴＳＨ对ＴＲＨ兴奋试验的应答反应呈超常强反应型，峰值呈持续状态，混合型次之，神经型呈弱或延迟反应型。另外还测定了８～１０岁不同组别的儿童８９例，ＴＲＨ兴奋试验结果分别为：２８例正常对照组的ＴＳＨ０、ＴＳＨ３０，各为３．５５±０．９８μＩＵ／ｍｌ、３０．４８±１１．４     

TRH兴奋试验在甲低症诊断与鉴别诊断中的价值

作者对１６例正常人和２１例甲状腺功能减低（甲低）患者进行了ＴＲＨ兴奋试验。在正常人，ＴＳＨ增值（△ＴＳＨ）平均为２２．０±８．６ｍＩＵ／Ｌ。１７例原发性甲低均呈过度反应（△ＴＳＨ均＞３６ｍＩＵ／Ｌ）．４例垂体性甲低患者，３例呈低反应（△ＴＳＨ＜３．０ｍＩＵ／Ｌ），１例为正常反应。本法对甲低的诊断与鉴别诊断是一种灵敏而可靠的方法。     

病毒性肝炎患者血清HGF和TGF—β1水平的临床意义

目的：探讨血清肝细胞生长因子（ｓＨＧＦ）和转化生长因子－β＿１（ＴＧＦ－β１）水平在病毒性肝炎患者中的临床意义。方法：选１３９例病毒性肝炎患者，以双抗体夹心ＥＬＩＳＡ检测ｓＨＧＦ，以改良ＭＶ１ＬＵ细胞生长抑制ＭＴＴ法检测ＴＧＦ－β＿１活性，同时检测其肝功能、肝纤维化、甲胎蛋白等指标。结果：各型病毒性肝炎患者ｓＨＧＦ水平及ＴＧＦ－β＿１活性均明显高于正常人水平（Ｐ值均＜０．０１）。ＴＧＦ－β１活性增高以肝硬化和重症肝炎最为显著（分别为９．４４±２．１７ｎｇ／ｍｌ和８．４２±２．５４ｎｇ／ｍｌ）。ｓＨＧＦ水平与ＴＧＦ－β＿１活性相关（Ｐ值＜０．０１）。结论：ｓＨＧＦ水平能反映患者肝细胞损伤及肝功能障碍程度，并与肝纤维化程度也可能有关。     

甲亢患者心钠素水平观察

作者对正常人（１１名）和甲亢未控制者（１４例）及甲亢经治疗后症状控制者（２８例）测定其心钠素（ＡＮＦ）水平，同时测定Ｔ３、Ｔ４。结果表明，甲亢患者ＡＮＦ水平明显高于正常，Ｔ３、Ｔ４也明显高于正常。甲亢经治疗后病情稳定时ＡＮＦ水平降至正常，Ｔ３、Ｔ４也降至正常，可以认为ＡＮＦ测定可作为甲亢的诊断指标之一和作为甲亢治疗中病情好坏的判断标准之一。     

Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-thyroxine therapy

A 15-month-old boy had clinical features of hyperthyroidism. In spite of elevated serum thyroid hormone levels (mean serum T4, 230 nmol/L; T3, 4.2 nmol/L), serum TSH levels ranged between 3.3-5.6 mU/L and rose to 35.4 mU/L after TRH stimulation. There was no abnormal serum thyroid hormone binding or any evidence of a pituitary tumor. The boy was treated with carbimazole for 6 months and became euthyroid. However, his thyroid size enlarged, and serum TSH rose to 45 mU/L. In an attempt to suppress TSH secretion, 3,5,3'-triiodothyroacetic acid was added to carbimazole in daily doses from 0.7-1.4 mg. This combined therapy failed to suppress TSH secretion (serum TSH, 10.2 mU/L) and led to recurrence of symptoms of hyperthyroidism. A trial using highly purified dextrothyroxine (contamination by L-T4, 0.05%) as sole therapy then was carried out. Serum TSH levels promptly declined to normal, both basally and after TRH stimulation (basal, 2.4 mU/L; peak, 13.8 mU/L). During a 24-month follow-up period, the boy remained euthyroid. Serum TSH levels remained in the normal range, as did his serum L-T4 levels (93 nmol/L). Complete remission was achieved using a 5-mg daily dose of D-T4. Temporary discontinuation of D-T4 led to prompt relapse of hyperthyroidism. Our patient's TSH hypersecretion appears to be due to selective pituitary resistance to thyroid hormones. Purified D-T4 effectively inhibited TSH secretion in this patient, without inducing significant side-effects, even when the daily dose was high. The cause of partial pituitary unresponsiveness to thyroid hormones is not known. We suggest that transport of thyroid hormones into the thyrotroph cells could be deficient in our patient.     

PROPRANOLOL IMPROVES THE IMPAIRED TSH RESPONSE TO TRH IN PATIENTS WITH AUTONOMOUSLY FUNCTIONING EUTHYROID MULTINODULAR GOITRE

Ten patients with autonomously functioning euthyroid multinodular goitre received propranolol (Inderal Retard 160 mg daily) for 4 weeks in order to investigate whether normalization of the TRH test or an increased TSH response to TRH could be obtained by decreasing serum T3 levels. Serum T3 decreased significantly after 2 and 4 weeks of propranolol administration. Serum T4 increased during this period, although the change was only significant after 4 weeks of propranolol. T3 resin uptake did not change. The TSH response to TRH increased significantly during the administration of propranolol. Mean delta TSH basally was 1.0, range 0-3.9 mU/l, and mean delta TSH after 4 weeks of propranolol was 2.4, range 0-9.3 mU/l. A strong correlation was found between the increase in delta TSH and the decrease in serum T3 after 4 weeks of propranolol. After withdrawal, delta TSH and T3 returned to premedication levels. Our data suggest that T3 is an important factor in the impairment of the TSH response to TRH in our patients. Normalization of the TRH test was, however, not obtained. These findings support the concept of subclinical hyperthyroidism in 'euthyroid' multinodular goitre with autonomous function.     

左旋甲状腺素钠治疗先天性甲状腺功能减退症的初始剂量研究

目的 探讨先天性甲状腺功能减退症(CH)左旋甲状腺素钠(L-T_4)替代治疗的初始剂量.方法对筛查确诊的CH患儿分为A(n=36)、B(n=51)、C(n=40)3组,分别采用L-T_4 10、8和6 μg·kg~(-1)·d~(-1) 3种不同的初始剂量治疗,分别在治疗后第2周、4-6周、8～12周复查血清TSH、T_4和FT_4水平,根据结果进行L-T_4剂量的个体化调整.12周后每3个月复查1次,随访2年.期间定期进行患儿体格发育评价,甲状腺超声检查、骨龄检测和智能发育测定.结果127例患儿治疗2周,(1)TSH水平,A、B组迅速下降至正常范围[(1.3±1.5)mU/L和(3.7±5.6)mU/L],两组间差异无统计学意义(P=0.28),A组中8例(22.2%)TSH下降到0.5 mU/L以下;C组TSH均未降至正常[(11.4±16.5)mU/L],与A、B组比较有显著性差异(P<0.01),其中10例(25.0%)TSH>10 mU/L,平均值为(34.0±19.2)mU/L.(2)T_4、FT_4水平迅速提高,A组有9例(25.O%)T_4>250 nmol/L;11例(30.6%)FT_4>45 pmol/L,达到正常值高限的1.5倍,并出现高甲状腺素血症,13例(36.1%)患儿分别表现腹泻、烦躁、多汗、哭吵不安等甲状腺功能亢进的临床症状.治疗12周后3组间TSH、T_4和FT_4水平无显著差异,L-T_4剂量也无显著差异.治疗随访2年,127例身高、体重均达到相应年龄的正常范围(x±s);腕部骨龄成熟程度达到相应年龄,3组无显著性差异;智力发育达到正常水平,3组间差异无统计学意义(均P>0.05).结论L-T_4初始剂量(8.0±0.5)μg·kg~(-1)·d~(-1)是我国先天性甲状腺功能减退症初始治疗比较安全、合理、有效的剂量.CH替代治疗时,L-T_4剂量必须个体化,保持甲状腺功能与其年龄相匹配的水平,应能保证其体格和智能的正常发育.     

The lack of nocturnal serum thyrotropin surge in patients with nontoxic nodular goiter may predict the subsequent occurrence of hyperthyroidism

TSH secretion, with particular regard to the nocturnal TSH surge, was evaluated in 115 subjects with non-toxic nodular goiter. All patients were clinically and biochemically euthyroid. After 18-36 months of follow-up (mean, 24 months), hyperthyroidism occurred in 21 (18%; group 1), while the remaining 94 remained euthyroid (82%; group II). The analysis of hormonal data at the time of first observation showed that the 2 groups had similar total and free T4 and T3 serum concentrations. Morning serum TSH values in group I were lower than those in group II patients (0.6 +/- 0.1 vs. 1.1 +/- 0.1 mU/L; P less than 0.001); this difference was even more striking for the nocturnal values (0.6 +/- 0.1 vs. 2.2 +/- 0.2 mU/L; P less than 0.0001); nocturnal values were significantly lower than morning values in group II, but not in group I. The mean peak TSH value after TRH was also significantly reduced in group I (5.5 +/- 0.4 vs. 9.2 +/- 0.7 mU/L; P less than 0.001). Morning TSH values in group II did not differ from those in controls (1.3 +/- 0.1 mU/L), whereas nocturnal and TRH stimulated peak TSH values were slightly but significantly lower. The nocturnal serum TSH values in control subjects were 62-390% higher than morning values. The nocturnal TSH surge was abolished in 18 of 21 (86%) group I patients and in 7 of 94 (8%) group II patients. TRH testing resulted in an absent or blunted TSH responses in 5 subjects in group I and 6 in group II. Analysis by the Galen and Gambino predictive model; comparing the abolition of the nocturnal TSH surge and the abnormal TRH test as predictors of the subsequent occurrence of hyperthyroidism, showed that the former had higher sensitivity (86% vs. 24%) and predictivity (72% vs. 45%). In conclusion, the results of the present study demonstrate that the evaluation of the nocturnal TSH surge may be useful in identifying patients with nontoxic nodular goiter in whom hyperthyroidism may eventually occur. Patients who lack the nocturnal serum TSH surge are more prone to develop thyroid hyperfunction; their thyroid status should, therefore, be more carefully and frequently monitored.     

EFFECTS OF THYROID HORMONES (T4, T3), BROMOCRIPTINE AND TRIAC ON INAPPROPRIATE TSH HYPERSECRETION

Inappropriate TSH hypersecretion was diagnosed in a 38-year-old woman (case 1) and in a 38-year-old man (case 2). Both of them had earlier been treated by ablative therapy for hyperthyroidism. The present diagnosis was based on elevated basal serum TSH levels despite elevated serum free thyroid hormone levels. Both of them had exaggerated TSH responses to TRH (peak value 240 mU/l in case 1 and 408 mU/l in case 2). Their albumin and prealbumin levels were normal. The serum TBG level was normal in case 1 but was elevated in case 2. Serum levels of alpha-subunits of TSH, and pituitary CT scans were normal. Despite mild clinical hyperthyroidism, peripheral indices of thyroid hormone action were normal. They had also relatives with apparent resistance to thyroid hormones. In view of the possibility that prolonged pituitary thyrotrophic stimulation is detrimental, various therapeutic approaches to suppress TSH levels were tried. Both T3 and T4 treatments lowered serum TSH levels, but were poorly tolerated. Acute administration of L-dopa or bromocriptine reduced serum TSH levels, but this was not seen during long-term therapy. TRIAC treatment lowered serum TSH levels, and the drug was well tolerated. Serum TSH responses to TRH were not blunted during T3, T4 or TRIAC treatments. Somatostatin also reduced serum TSH levels, but did not potentiate the effect of low dose T3 therapy. Our results suggest that the patients had unbalanced pituitary and peripheral thyroid hormone resistance, predominantly at the pituitary level. Of the drugs studied, TRIAC seemed to be the most suitable therapy.     

INAPPROPRIATE THYROTROPHIN SECRETION, INCREASED DOPAMINERGIC TONE AND PRESERVATION OF THE DIURNAL RHYTHM IN SERUM TSH

A patient presented with mild hyperthyroidism, elevated serum T4 and T3, and an inappropriately raised serum thyrotrophin (TSH). There was no evidence of pituitary tumour (alpha-subunit secretion and CT scan of the pituitary were normal). The TSH response to TRH was greater than normal. The elevated TSH was suppressed by oral triiodothyronine (100 micrograms daily for 10 d). The normal diurnal variation of TSH was preserved. Intravenous injection of the dopamine receptor blocking agent domperidone led to a greater than normal elevation in TSH (maximum increments 18-20 mU/l). This increased dopaminergic tone was similar in studies carried out in the morning and late evening. The dopamine agonist bromocriptine (2.5 mg twice daily) failed to suppress serum TSH either acutely or over 6 weeks. The circadian rhythm was unaltered by this treatment. Basal serum prolactin levels were normal, and responded appropriately to TRH, domperidone and bromocriptine. These observations indicate that dopamine does not control the diurnal variation of TSH in nontumoral TSH-mediated hyperthyroidism. The increased dopaminergic tone demonstrated may be secondary to the primary failure of pituitary-thyroid feedback in the condition.     

Applications of a new chemiluminometric thyrotropin assay to subnormal measurement

A new immunochemiluminometric TSH assay (ICMA) was shown to offer improved analytical (+2 SD of zero) and functional (20% interassay coefficient of variation) sensitivity [0.003 vs 0.045 +/- 0.005 (+/- SE; range, 0.01-0.07); 0.018 vs. 0.23 +/- 0.02 (range, 0.10-0.35, mU/L); analytical vs. functional sensitivity limit for the ICMA vs. 10 other TSH immunometric assays, respectively]. The ICMA was used to study the physiological relationship between serum TSH and free T4 [as reflected by free T4 index (FT4I)] values at both steady state and 14 days after acute pharmacological T4 administration (3 mg oral T4 load plus 0.3 mg daily). At steady state, an inverse log/linear relationship was found between serum TSH and FT4I values (log TSH = 2.56 - 0.022 FT4I; r = 0.84; P less than 0.001). Ten to 14 days after acute T4 suppression in 5 euthyroid subjects, serum TSH/FT4I levels had plateaued after decreasing in parallel to the slope of the steady state relationship, suggesting that the degree of T4 suppression of TSH can be predicted from an individual's pituitary TSH/free T4 set-point and the magnitude of the serum T4 elevation achieved. Ambulatory and hospitalized patient sera, previously identified as having low (less than 0.1 mU/L) TSH levels by a less sensitive assay, were restudied by the TSH ICMA. Normal TSH values ranged from 0.39-4.6 mU/L, whereas the majority of hyperthyroid patients [52 of 54 (96% ambulatory) and 22 of 23 (96%, hospitalized)] had undetectable (less than 0.005 mU/L), basal TSH levels and absent TRH stimulated TSH responses. In contrast, most (32 of 37; 86%) of hospitalized nonhyperthyroid patients with low (less than 0.1 mU/L) TSH values due to nonthyroidal illness or glucocorticoid treatment had detectable (greater than 0.01 mU/L) basal and TRH stimulated TSH levels. The positive relationship between basal and TRH-stimulated TSH levels was shown to extend down to the detectability limit of the assay (0.005 mU/L), which further supported the authenticity of the subnormal TSH ICMA measurements. The new TSH ICMA is considered to represent the first of a third generation of clinical TSH assays, since it has a functional (interassay) sensitivity that is 2 orders of magnitude greater than that of typical first generation TSH RIAs and 1 order of magnitude greater than current second generation TSH immunometric methods. Such third generation TSH assays will facilitate both the optimization of T4 therapy as well as the diagnosis of hyperthyroidism in hospitalized patients with nonthyroidal illness.     

Absence of receptors for thyrotropin (TSH)-releasing hormone in human TSH-secreting pituitary adenomas associated with hyperthyroidism

In patients with TSH-secreting pituitary adenomas associated with hyperthyroidism, TSH secretion usually does not respond to exogenous TRH stimulation. To determine the basis for this unresponsiveness, we studied TRH binding to the membranes of two such TSH-secreting pituitary adenomas. The patients, a 28-yr-old man and a 60-yr-old woman, had clinical and biochemical hyperthyroidism with increased serum TSH levels (15.7 and 14 mU/L, respectively; normal range, 1.1-7.2) and alpha-subunit to TSH molar ratios greater than 1 (2.4 and 1.7, respectively). Neither patients had an increase in serum TSH in response to TRH (200 micrograms, iv). Immunocytochemistry of the two adenomas, removed by transsphenoidal surgery showed a pure population of thyrotropic cells. Binding studies were performed by incubation of tumor cell membrane suspensions with increasing amounts of [3H]TRH. Two PRL-secreting adenomas and one normal human pituitary were used as controls. The characteristics of the TRH-binding sites from the control tissues were similar to those previously reported (Kd, 56, 30, and 49 nM; maximum binding, 187, 46, and 94 fmol/mg protein, respectively). In contrast, no specific TRH binding was found in the two TSH-secreting adenomas. We conclude that the unresponsiveness of TSH after TRH administration is related to the absence of specific TRH-binding sites in these thyrotropic tumors.     

Arginine stimulates growth hormone secretion by suppressing endogenous somatostatin secretion

To determine how arginine (Arg) stimulates GH secretion, we investigated its interaction with GHRH in vivo and in vitro. Six normal men were studied on four occasions: 1) Arg-TRH, 30 g arginine were administered in 500 mL saline in 30 min, followed by an injection of 200 micrograms TRH; 2) GHRH-Arg-TRH, 100 micrograms GHRH-(1-44) were given iv as a bolus immediately before the Arg infusion, followed by 200 micrograms TRH, iv; 3) GHRH test, 100 micrograms GHRH were given as an iv bolus; and 4) TRH test, 200 micrograms TRH were given iv as a bolus dose. Blood samples were collected at 15-min intervals for 30 min before and 120 min after the start of each infusion. Anterior pituitary cells from rats were coincubated with Arg (3, 6, 15, 30, and 60 mg/mL) and GHRH (0.05, 1, 5, and 10 nmol/L) for a period of 3 h. Rat GH was measured in the medium. After Arg-TRH the mean serum GH concentration increased significantly from 0.6 to 23.3 +/- 7.3 (+/- SE) micrograms/L at 60 min. TRH increased serum TSH and PRL significantly (maximum TSH, 11.1 +/- 1.8 mU/L; maximum PRL, 74.6 +/- 8.4 micrograms/L). After GHRH-Arg-TRH, the maximal serum GH level was significantly higher (72.7 +/- 13.4 micrograms/L) than that after Arg-TRH alone, whereas serum TSH and PRL increased to comparable levels (TSH, 10.2 +/- 3.0 mU/L; PRL, 64.4 +/- 13.6 micrograms/L). GHRH alone increased serum GH to 44.9 +/- 9.8 micrograms/L, significantly less than when GHRH, Arg, and TRH were given. TRH alone increased serum TSH to 6.6 +/- 0.6 mU/L, significantly less than the TSH response to Arg-TRH. The PRL increase after TRH only also was lower (47.2 +/- 6.8 micrograms/L) than the PRL response after Arg-TRH. In vitro Arg had no effect on basal and GHRH-stimulated GH secretion. Our results indicate that Arg administered with GHRH led to higher serum GH levels than did a maximally stimulatory dose of GHRH or Arg alone. The serum TSH response to Arg-TRH also was greater than that to TRH alone. We conclude that the stimulatory effects of Arg are mediated by suppression of endogenous somatostatin secretion.