Synthetic thyrotropin-releasing factor (TRF), L-pyroglutamyl-L-histidyl-L-proline amide, has been administered intravenously to the cases with primary hypothyroidism, thyrotoxicosis and patients receiving desiccated thyroid powder in doses ranging from 30 to 50 mg. Changes in plasma TSH levels, PBI and T₃ resin sponge uptake (T₃RSU) were estimated. TRF in doses of 50-200 μg stimulates a rapid rise in plasma TSH in all of the normal subjects. No rise in plasma TSH level occurred following 100 Jag of TRF in patients receiving desiccated thyroid powder. Primary hypothyroidism showed high resting TSH levels and exaggerated TSH response to TRF, 2 types of TRF that induced TSH response were observed in 26 cases with untreated thyrotoxicosis. The one was blunted TSH response and the other was suboptimal TSH response to TRF. When thyrotoxic patients became enthyroid state following treatment, almost normal TSH response were observed after TRF administration except a few cases with longstanding thyrotoxicosis.

View full abstract

Insuin-hypoglycemia and arginine monochloride infusion are potent stimuli for the secretion of growth hormone (GH) from the pituitary. It has been supposed, however, that these two stimuli may act on different sites in the GH stimulatory system, because of the difference in the effect of glucose or corticosteroids, and in the overlapping effect on other pituitary hormones of these stimuli. Should this be so, some cases of dissociation in the responses to these stimuli could be expected in a mass of clinical cases.
Fifty-nine patients with various conditions were studied with both stimulatory tests. Each test was performed after overnight fasting and bed rest. In the arginine test, arginine monochloride, 0.5 g/kg body weight in 10% solution, was infused for over 30 minutes. Regular insulin, 0.1 U/kg body weight, was injected as a single shot in the insulin test. In each test, blood was take every 30 minutes for 150 minutes from 30 minutes before the injection or the beginning of the infusion.
Plasma GH levels were determined by double-antibody radioimmunoassay with NIH-GH-HS1147BC as standard. All results were neglected when the basal GH level was over 5 ng/ml in each test or the blood sugar nadir was over 50 mg/100 ml in insulin test.
In 34 healthy subjects, the mean peak plasma GH level in the arginine test was 19.8 ng/ml with a two-standard deviation (2σ) range of 9.6-40.9 and that for insulin test in 30 cases was 26.6 with a 2σ-range of 11.8-59.7 (calculated by logarithmic conversion; Figure 1). Responses with peak values below 2a-limit were considered to be lower than normal. The reproducibility of these two tests was shown to be fairly good (Figures 2 and 3).
The results are summarized in Figure 4.
Eleven cases with primary hypopituitarism, 10 with chromophobe adenoma of the pituitary and 1 with Sheehan's syndrome were all unresponsive except one with chromophobe adenoma who showed the near-the-limit responses.
Out of 12 cases of secondary hypopituitarism, 4 with craniopharyngioma, 2 with ectopic pinealoma, each one with third ventricle tumor, Schüer-Christian's disease and basal meningitis were unresponsive in both tests. One with third ventricle tumor (ependymoma) causing pubertas praecox showed normal response to both stimuli, while each one with hypothalamic glioma causing pubertas praecox (8-year-old girl), benign aqueductus stenosis (22-year-old female) showed normal response only to arginine.
Twelve cases of hypopituitarism due to unknown etiology had low responses; one of them showed near-the-limit response to arginine.
Out of 6 primary hypothyroid patients, 2 had low responses in both tests, while 3 responded normally only to arginine. One of the latter, a hypothyroidal dwarf of 17-year-old girl, had a better response to arginine after 20 days of thyroid powder therapy and restored the response to insulin after 3.5 months of therapy.
Four cases of Turner's syndrome responded lower than normal to hypoglycemia but 3 of them had normal responses to arginine.
Three of 5 cases of Cushing's syndrome, 4 with adrenal adenoma and 1 with bilateral adrenal hyperplasia, had lower responses to both tests, while 2 showed normal response only to arginine. One of the latter (adenoma) restored the response to arginine first and then to hypoglycemia after adrenalectomy.
All 6 cases of primordial dwarfs showed responses within normal range in both tests. The peak levels were higher in hypoglycemia than in arginine test in 5 cases.
Three cases of suspected, but not definitely diagnosed, anorexia nervosa (Figure 5) had low responses to insulin but normal to arginine.
Thus, the absolute values of the peak GH levels were higher in insulin test in normal subjects and 5 of 6 cases of primordial dwarfism, but higher in arginine test in all these dissociated cases.

View full abstract

With the wide usage of the thyroidal radioiodine uptake test in the evaluation of thyroid function, it is important to define some of the limitations and sources of error in this procedure. One common problem is the artifactual lowering of the thyroidal radioiodine uptake which follows administration of various iodine-containing compounds. A number of studies on the effect of some cholecystographic, pyelographic and bronchographic contrast media and stable iodine on the thyroidal ¹³¹-I uptake has resulted in conflicting information. Moreover, there have been no accurate reports concerning the effect of iodine-containing compounds on the thyroidal uptake of radioactive iodine except for seaweeds which are commonly taken as food in Japan.
In this study the duration of interfering effect of various iodine-containing compounds on the thyroidal 24-hr. ¹³¹-I uptake was determined. The iodine-containing compounds investigated were potassium iodide, Maryngin-M, Entero-Vioform (Iodochloroxy-Quinoline), Telepaque (Iodopanoic acid, for oral cholecystography), Biloptin (for oral cholecystography), Biligrafin (Iodipamide Sodium, for venous cholecystography), Urografin (Diatorizoate Sodium, for intravenous pyelography, angiography, arthrography, fistelography and discography), Moljodol (for hysterosalpingography and myelography), Endografin (for hysterosalpingography) and Myodil (for myelography and fistelography).
The subjects employed were 180 euthyroid patients and 5 cases of hyperthy-roidism without any hepatocholecystic and renal dysfunction. None had any indication of thyroid abnormality and there was no history of taking interfering medicinal or chemical agents in euthyroid subjects. Prior to the uptake test, intake of any form of iodine was restricted for 7 days and the uptake was measured before and after administration of a drug. Follow-up studies were performed at varying intervals following administration of the iodine-containing compounds. After the basic study, all data for radio-iodine content in the thyroid were corrected for the amount of ¹³¹-I present in the thyroid just before each new test dose. To further minimize the error resulting from the thyroid residual of ¹³¹-I, successive test doses were made progressively larger.
In the euthyroid subjects given 1 to 1000 mg of potassium iodide orally three times a day, it was observed that the uptake recovered within 48 hrs with 5 mg, within 72 hrs with 100 mg and within 4 days with 1000 mg of potassium iodide, respectively, although no inhibition was observed with 1 mg. In 9 patients given 3 gm of Marygin-M (I : 2.7 mg) three times a day, the uptake returned to the preadministration level about 2 days after administration. In 8 patients given 1.5 gm of Entero-Vioform (I : 579 mg) three times a day, the uptake returned to the previous level about 7 days after administration. In 25 patients given 6 tables (3.0 gm) of Telepaque (I : 1.98 gm) in a single dose, the uptake recovered within normal range 3 weeks after administration, while with 6 tables (3.0 gm) of Biloptin (I : 1.86 gm) at recovered 2 weeks after administration. In all 5 cases with intravenous administration of 20 ml of 30% (I : 3.0 gm) and 50% (I : 5.0 gm) of Bili-grafin, the uptake returned to normal range about one week after daministration, respectively. In all 7 cases with intravenous and intraarterial administration of 20 and 30 ml of 76% Urografin (I : 7.4 and 11.1 gm), the uptake recovered to the preadministration level 4 days after administration, respectively. In all 3 patients who underwent arthrography (2-8 ml of 76% Urografin, I : 0.74-2.96 gm), the uptake returned to normal range about 38 days after administration. In 2 patients who underwent fistelography (5-15 ml of 76% Urografin, I : 1.05-5.55 gm), the uptake returned to normal range 23 days after administration,

View full abstract

It has long been known that the administration of iodine and iodine-containing compounds raises the serum level of protein-bound iodine (PBI) even long after discontinuing the administration. A number of studies on the effect of some cholecystographic and pyelographic contrast media on the PBI have been done abroad, but resulted in conflicting information. Moreover, there have been no accurate reports concerning the effect of iodine-containing compounds on the PBI in Japan. Therefore, it was thought of interest to determine the duration of interfering effect of various iodine-containing compounds on the PBI in this study.
The substances investigated were Urografin (Diatorizoate Sodium, for intravenous pyelography and angiography), Moljodol (for hysterosalpingography), Biloptin and Telepaque (for oral cholecystography).
Subjects employed were 88 euthyroid patients and 6 cases of hyperthyroidism without any hepatocholecystic and renal dysfunction. None had any indication of thyroidal abnormality and there was no history of taking interfering medicinal or chemical agents in euthyroid subjects. The PBI was measured before and after administration of a contrast medium. The follow-up studies were performed at varying intervals after administration.
In all 15 euthyroid patients who underwent intravenous pyelography with 20 ml of 76% Urografin (I : 7.4 gm) and 4 patients who underwent angiography with 30 ml of 76% Urografin (I : 11.1 gm), the serum level of PBI recovered to the normal range 2 days after administration, respectively. In 41 sterile but euthyroid women with no obstruction in the tubular pathways, the hysterosalpingography with 10-20 ml of 40% Moljodol (I : 5.32-10.64 gm) inhibited the PBI for approximately one year and a half, although the series as a whole exhibited major variations. In 17 patients given 6 tablets (3.0 gm) of Telepaque (for oral cholecystography, I : 1.98 gm) in a single dose, the PBI recovered within normal range 2 months after administration, while in 11 cases with 6 tablets (3.0 gm) of Biloptin (for oral cholecystography, I : 1.86 gm), the PBI recovered 3 months after administration.
In 6 cases of hyperthyroid patients who had taken 6 tablets of Telepaque in a single dose for oral cholecystography, PBI recovered to the preadministration level about 1-2 weeks after administration. These hyperthyroid patients had been treated with anti-thyroid drugs for a few weeks, but the result of thyroid function tests, such as serum thyroxine level, ¹³¹-I triiodothyronine resin sponge uptake and BMR were within thyrotoxic range.
It was concluded that the duration of interfering effect of various iodine-containing compounds on the PBI were defined depending on the sort of, way of administration of, and the content of iodine in the compound and the absorbtion of iodine-containing compound by oral administration, and, that the duration of the interference was shorter in hyperthroid patients than in euthyroid subjects. Moreover, the duration of interference on PBI in euthyroid subjects were shorter than that on ¹³¹-I uptake in the case of Urografin (for intravenous pyelography and angiography) administration, about the same as in the case of Moljodol (hysterosalpingography) administration, but longer in cases of Biloptin and Telepaque (for oral cholecystography).

View full abstract

Although many factors are thought to be responsible for regulating pituitary TSH secretion, TSH release is generally under the control of TRF and serum thyroxine concentration.
However, TSH release is influenced by other hormone concentrations in the serum such as estradiol and especially glucocorticoid. Influence of glucocorticoid administration or increased serum corticoid concentration on TRF that induced TSH release was observed in cases with long-term corticosteroid administration or Cushing's syndrome.
TRF that induced TSH release was inhibited in cases with long-term glucocorticoid administration such as chronic nephritis, bronchial asthma, bronchogenic carcinoma and sarcoidosis. These cases had been administrated 8,000 mg or more of glucocorticoid in cortisol equivalent.
Distinct plasma TSH increase by TRF were observed in cases with short-term or intermittent glucocorticoid administration.
No or a slight rise in plasma TSH levels occurred following TRF in patients with Cushing's syndrome who had adrenocortical adenoma.
Normal TSH increase following increased doses of TRF was obtained from cases with the above-mentioned long-term corticoid administration.
Glucocorticoid treatment in large doses and increased serum corticoid concentration seemed to inhibit plasma TSH increase following certain doses of TRF.

View full abstract