AMIODARONE AND THYROID HORMONE EFFECTS ON ANTERIOR PITUITARY HORMONE GENE EXPRESSION

Amiodarone therapy results in marked changes in circulating thyroid hormone and TSH concentrations in man. In the present study we have demonstrated that amiodarone treatment of the rat increases serum TSH and pituitary cytoplasmic concentrations of TSH beta and alpha subunit messenger RNAs (mRNAs) and reduces PRL mRNA as measured by cytoplasmic dot hybridization with specific complementary (c) DNA probes. The fall in circulating TSH and TSH mRNA resulting from thyroid hormone treatment was less marked in animals receiving amiodarone in addition to T3 and T4. In contrast, in the hypothyroid state, increases in serum TSH, TSH beta and alpha mRNA, and reductions in PRL and GH mRNA were less marked in rats treated with amiodarone. In studies of rat anterior pituitary cells in primary monolayer culture we demonstrated a direct effect of amiodarone on PRL gene expression which was antagonized by T3. Changes in circulating thyroid hormone concentrations and deiodination of T4 and T3 induced by amiodarone in vivo may be important in the regulation of pituitary hormone gene expression but we have, in addition, shown a direct interaction between amiodarone and T3 effects on the anterior pituitary cell.     

GONADOTROPHIN AND ALPHA SUBUNIT SECRETION BY HUMAN ''FUNCTIONLESS'' PITUITARY ADENOMAS IN CELL CULTURE: LONG TERM EFFECTS OF LUTEINIZING HORMONE RELEASING HORMONE AND THYROTROPHIN RELEASING HORMONE

The long-term effects of LHRH and TRH on gonadotrophin alpha subunit, FSH and LH secretion by cell cultures of four human chromophobic pituitary tumours have been examined. The tumours derived from one male and three female patients who presented because of visual disturbance but had no evident endocrine symptoms. Subsequent serum hormone analysis showed the FSH to be high in the male but low or normal in the post-menopausal females whereas LH levels were low in all patients. In culture, basal hormone secretion could be maintained for periods up to 63 d. All tumours secreted alpha subunit and FSH, but much lower amounts of LH. Addition of LHRH or TRH for a period of 12 to 41 d showed that alpha subunit, FSH and LH secretion were stimulated by LHRH from one tumour, by LHRH and TRH from two tumours. There was always a rapid decline in the LH secretion. The tumour which secreted FSH predominantly was stimulated by TRH. We conclude that human pituitary 'functionless' adenomas can secrete gonadotrophin alpha subunit and FSH in vitro and that secretion can be stimulated during long term releasing hormone experiments. LH secretion, however, cannot be maintained.     

PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONE

A 32-year-old Caucasian male, clinically euthyroid, with paranoid schizophrenia and granulocytopenia, had elevated total and free serum T4 and T3; serum TSH was normal (2.7 +/- 0.7 micronU/ml). There was no goitre present, no evidence of Graves' disease, and no evidence of pituitary tumour. He had a normal response to methyl-TRH, with a TSH increment of 14.6 micronU/ml, T3 increment of 212 ng/dl, and T4 increment of 4.7 microgram/dl; baseline value and decreased the TSH increment in response to methyl-TRH. T3 therapy (100 microgram/day) decreased the thyroidal radioactive iodine uptake to less than half the baseline prolactin was normal with a normal response to methyl-TRH to 4.1 micronU/ml. Iodine therapy caused an increase in his baseline TSH with an increase in the TSH response to TSH. The metabolic clearance rates (MCR) and production rates (PR) of T3 and T4 were increased. Baseline serum levels of glycoprotein hormone alpha-subunit were normal and showed a slight increase in response to methyl-TRH, similar to normal subjects. This patient has evidence of partial pituitary and peripheral resistance to thyroid hormone; his only evidence for hyperthyroidism is the elevated MCR and PR of T3 and T4.     

GLYCOPROTEIN HORMONE α SUBUNIT SECRETION BY PITUITARY ADENOMAS: INFLUENCE OF EXTERNAL IRRADIATION

In ninety-nine patients with pituitary adenomas, forty-six with acromegaly, the serum level of the glycoprotein hormone alpha subunit was elevated in eighteen cases. Thirteen of these were acromegalic and one had an FSH-producing tumour. Alpha levels varied little during the day, from one day to the next and over a 6 month period. In twenty-five patients with a variety of other hypothalamic-pituitary disorders examined, one patient with a craniopharyngioma had a mildly elevated alpha level. External pituitary irradiation was followed by an acute and often transient fall in alpha level in several of these patients. Of the fifty-four patients with pituitary adenomas who had received external irradiation before testing, only five had elevated alpha subunit levels compared with thirteen patients of the forty-five who had not been irradiated. This difference in incidence of elevated alpha level was statistically significant (P less than 0.025). We conclude that external irradiation may reduce alpha subunit level chronically in many patients with pituitary adenoma.     

EFFECT OF FENOLDOPAM, A DOPAMINE D-1 RECEPTOR AGONIST, ON PITUITARY, GONADAL AND THYROID HORMONE SECRETION

The influence of fenoldopam, a dopamine (DA) D-1 receptor agonist, on basal and GnRH/TRH stimulated PRL, GH, LH, TSH, testosterone and thyroid hormone secretion was studied in nine normal men. All men received 4-h infusions of either 0.9% saline or fenoldopam at an infusion rate of 0.5 microgram/kg min, 12-16 ml/h, adjusted according to weight. After 3 h of infusion, 50 micrograms GnRH and 100 micrograms TRH was given i.v. Blood samples were collected every 15 min from 1 h before to 1 h after the infusion for a total of 6 h for measurements of PRL, LH, FSH, GH, TSH, testosterone, T4 and T3. The median PRL concentration increased significantly (P less than 0.01) to 128%, range 87-287, of preinfusion levels, compared to the decline during control infusion (85%, 78-114). Basal TSH levels declined significantly to 71% (60-91) during fenoldopam compared with 82% (65-115) during control infusion (P less than 0.05). Basal LH, FSH, GH and thyroid hormones were similar during fenoldopam and control infusions (P greater than 0.05). The LH response to GnRH/TRH was significantly (P less than 0.02) increased by fenoldopam infusion. Basal and stimulated testosterone concentration was lower during fenoldopam (P less than 0.01) infusion compared with control. Other hormones were similar after GnRH/TRH stimulation during fenoldopam and saline infusions. These results suggest that DA D-1 receptors are involved in the modulation of pituitary hormone secretion. We suggest that the effect of fenoldopam on PRL and TSH is mainly at the hypothalamic level. Regarding the effect on LH concentrations, an additional direct effect of fenoldopam on testosterone regulation can not be excluded.     

GROWTH HORMONE SECRETING PITUITARY ADENOMAS ARE HETEROGENEOUS IN CELL CULTURE AND COMMONLY SECRETE GLYCOPROTEIN HORMONE α-SUBUNIT

Cell culture methods were used to assess whether human pituitary adenomas secreting GH and associated with clinical acromegaly also secreted the structurally unrelated glycoprotein hormone alpha-subunit. Thirty-two tumours, together with peri-adenomatous tissue from two of them and three normal pituitaries were studied. Anterior pituitary hormones were measured by radioimmunoassay and included PRL, TSH, LH, FSH, and ACTH, as well as GH and alpha-subunit. Normal pituitary tissues secreted all hormones assayed. All 32 tumours secreted GH ranging from 241 to 5556 ng/2 X 10(5) cells/24 h and 12 (37.5%) secreted alpha-subunit in amounts which could not be accounted for by cross-reaction of other hormones or contamination by normal pituitary tissue, and which ranged from 10.3 to 73.5 ng/2 X 10(5) cells/24 h. Ten other tumours also secreted alpha-subunit but in very small amounts, not exceeding 1.8 ng/2 X 10(5) cells/24 h. PRL was secreted from 21 tumours (66%), and small amounts of other hormones, chiefly LH and TSH, were occasionally secreted from tumours. These cell culture studies would suggest that pituitary adenomas causing acromegaly are hormonally heterogeneous and that PRL and glycoprotein alpha-subunit are commonly detected in addition to GH.     

EFFECTS OF CIMETIDINE ON PITUITARY FUNCTION: ALTERATIONS IN HORMONE SECRETION PROFILES

Cimetidine, an H₂ receptor antagonist, was given for 6 weeks to six normal male volunteers to study the effects on pituitary, adrenal, thyroid, and testicular hormone secretion. Patients were studied before (day 1) and after (day 42) cimetidine (300 mg four times daily) therapy, and four of the six were restudied after discontinuing cimetidine for 1 month (day 72). Basal TSH concentrations and responses to TRH administration as well as T3 RIA and T4 resin uptakes did not change during or after cimetidine therapy. The diurnal rhythm of plasma cortisol and maximum cortisol response to insulin (0·15 u/kg) were similar on days 1 and 42, but urinary free cortisol excretion fell 31% (P < 0·01). Response of GH to exercise, 100 g carbohydrate ingestion and insulin were unchanged, but mean nocturnal GH secretion decreased 33% (P < 0·025) on cimetidine, and returned to baseline on day 72. The 24-h plasma prolactin profile was unchanged as was the prolactin response to insulin and TRH stimulation. Plasma FSH was not altered, but mean LH concentrations decreased 20% on cimetidine and continued to decline (45% of day 1 levels) after discontinuation of cimetidine (P < 0·01). Spontaneous LH pulse amplitude declined slightly on day 42, but became significantly lower on day 72 (P < 0·01) while pulse frequency increased modestly on day 72 (P < 0·05). Peak LH responses to gonadotropin-releasing hormone were also reduced on cimetidine therapy (P < 0·02). Plasma testosterone concentrations did not change but plasma oestradiol concentrations were 38% lower (P < 0·025) after cimetidine was discontinued. H₂ histamine receptors are involved in the control of multiple hormone secretory patterns and blockade of these receptors by cimetidine alters hormone profiles. These changed patterns have to be considered in the interpretation of hormone measurements in patients receiving cimetidine therapy.     

COMPARISON BETWEEN DOSE-RESPONSES OF PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE TO TWO DIFFERENT HISTAMINE H2-RECEPTOR ANTAGONISTS IN NORMAL MEN

The effects of the histamine H2-receptor antagonists, ranitidine and cimetidine on prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) were studied in six normal males. Intravenous bolus injections of saline and of 50, 100, and 200 mg ranitidine and 300 mg cimetidine were tested. Ranitidine (100 and 200 mg) and cimetidine (300 mg) caused a significant increase in PRL secretion, whereas saline and ranitidine (50 mg) did not. TSH and GH secretion were unaffected by all doses. A dose-response relationship between ranitidine and PRL was established, and a dose of 65 mg ranitidine was found to be the minimal effective PRL-releasing dose. Plasma ranitidine concentration was measured by specific RIA. The results indicate an effect of H2-receptor antagonists on physiological functions in the control of PRL secretion. Histamine, therefore, may play a role in the regulation of PRL secretion.     

INTERACTION OF THYROTROPHIN RELEASING HORMONE AND THE ENKEPHALIN ANALOGUE DAMME ON PITUITARY HORMONE SECRETION

Because TRH counteracts the inhibitory effect of opiate peptides on LH secretion in cultured cells from normal pituitaries, six normal postmenopausal women were studied to determine whether TRH interacts in vivo with opioid peptides in the regulation of pituitary hormone secretion. At two different times a constant 3 h infusion of either saline or TRH (5 micrograms/min) was initiated. At 60 min a 250 micrograms bolus of the opiate agonist peptide D-Ala2-MePhe4-met-enkephalin-0-ol (DAMME) was injected in one of the two saline and TRH infusion tests. The four treatments, i.e. saline infusion alone, saline infusion with a DAMME bolus, TRH infusion alone; and TRH infusion with DAMME bolus were given at random with an interval of at least 7 d. Blood samples were taken every 15 min during the 3 h study. DAMME induced a significant fall (P less than 0.05) in serum LH (from 35 +/- 8.5 to 18.3 +/- 5.1 mIU/ml) (mean +/- SEM) without significantly affecting FSH levels (from 29 +/- 11.2 to 26.9 +/- 12.4 mIU/ml). These changes were not antagonized by the continuous infusion of TRH. PRL had a monophasic response pattern to continuous isolated TRH infusion; the basal levels increased from 4.2 +/- 1.2 to 24.5 +/- 6.8 ng/ml at 30 min and then slowly decreased with a plateau from 90 min until the end of the study. DAMME administration at 60 min induced a significant second peak of PRL secretion (44 +/- 6.5 ng/ml) 30 min later (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

GLUCOCORTICOIDS AND GLUCOSE METABOLISM: HEPATIC GLUCOSE PRODUCTION IN UNTREATED ADDISONIAN PATIENTS AND ON TWO DIFFERENT LEVELS OF GLUCOCORTICOID ADMINISTRATION

Plasma glucose, insulin levels and hepatic glucose production rates were studied after an overnight fast in six Addisonian patients in three different conditions: off replacement treatment, on substitution therapy and on high-dose glucocorticoid treatment. For comparison eight normal subjects were evaluated in basal conditions. Fasting plasma glucose and hepatic glucose production did not change significantly with either level of glucocorticoid treatment when compared to the untreated state and the normal controls, but there was a significant increase in plasma glucose levels in the high-dose cortisone-treated Addisonian patients when compared to the untreated state. Insulin levels were significantly lower in the untreated state and significantly higher in the high dose-treated patients when compared to the normal controls. It is suggested that in these experimental conditions the peripheral actions of glucocorticoids are predominant over the hepatic effects by virtue of their ability to produce secondary changes in insulin levels, keeping the hepatic glucose production constant.     

COMPARATIVE EFFECTS OF SODIUM IPODATE AND IODIDE ON SERUM THYROID HORMONE CONCENTRATIONS IN PATIENTS WITH GRAVES'' DISEASE

Patients with thyrotoxic Graves' disease were treated daily for 10 d with 1 g sodium ipodate, an iodine rich X-ray contrast agent which impairs outer ring (5'-) deiodination of T4 to T3, or with 12 drops of a saturated solution of potassium iodide (SSKI). T4, T3 and reverse T3 (rT3) concentrations were measured before, during, and 5 and 10 d after the administration of each drug. SSKI therapy induced a decrease in the serum T4 concentration from 14.7 +/- 1.3 microgram/dl (mean +/- SE) to a nadir of 7.9 +/- 0.9 on days 9 and 10 of therapy, all values reaching the normal range by day 9; a decrease in the serum T3 concentration from 402 +/- 43 ng/dl to a nadir of 143 +/- 20 on day 10, remaining elevated in all patients until day 5 and decreasing into the normal range in all except one patient on days 9 and 10; and no change in the serum rT3 concentration. Serum T4 and T3 concentrations returned to baseline values 10 d after withdrawal of SSKI. In contrast sodium ipodate therapy induced only a modest decrease in the serum T4 concentration from 15.1 +/- 0.7 micrograms/dl to a nadir on day 9 of 11.3 +/- 1.0 and serum T4 remained above the normal range in most patients until day 8; a striking and rapid decrease (within 12 h) in ther serum T3 concentration from 340 +/- 36 ng/dl to mean values ranging from 79 to 85 during the last 5 d of therapy, with most values below the normal range during the last 3 d; and a marked increase in the serum rT3 concentration from 111 +/- 15 ng/dl to a peak value of 376 +/- 59 on day 5.(ABSTRACT TRUNCATED AT 250 WORDS)     

EFFECTS OF ETHINYLOESTRADIOL ON PLASMA LEVELS OF PITUITARY GONADOTROPHINS, TESTICULAR STERIODS AND SEX HORMONE BINDING GLOBULIN IN NORMAL MEN

Daily measurements of plasma FSH, LH, prolactin, testosterone, 17β-oestradiol and sex hormone binding globulin (SHBG) activity were made in eight healthy, normal men during treatment with oral ethinyloestradiol (EE₂) in a dose of 30 μg/day for 5 days following a 5-day control period. No significant changes in plasma levels of FSH and prolactin during oestrogen treatment occurred. In contrast, plasma concentrations of both LH and testosterone showed a biphasic pattern. Following an initial suppression during the first 3 days of oestrogen treatment both LH and testosterone increased again to baseline values despite continuation of oestrogen administration. The secondary rise of both hormones was associated with (and probably resulted from) a nearly 100% increase in the plasma concentration of SHBG binding activity, and hence reduction of free testosterone index (FTI). Unlike testosterone, plasma 17β-oestradiol during EE₂ administration did not show a biphasic pattern, but a progressive decline that was positively correlated with the fall in FTI. The rapidity of onset and magnitude of the observed rise in SHBG levels emphasizes the need for measurement of this binding protein (or the free testosterone fraction) in studies on feedback regulation of gonadotrophins employing exogenous EE₂ in human males. The observed increase of SHBG to supraphysiological values suggests that currently employed EE₂ doses in such studies may be less ‘physiologic’ than is often assumed.     

过量氟和硒对大鼠垂体,甲状腺,甲状旁腺的影响

为观察过量氟对大鼠垂体、甲状腺、甲状旁腺的影响及硒的保护作用，选用Ｗｉｓｔｒａｒ大鼠饮用３０ｍｇ／Ｌ与５０ｍｇ／Ｌ高氟水，同时设高氟水加富硒饲料组。自实验第４个月光镜下见甲状腺呈现弥漫增生性改变，８个月和１４个月出现增生和过度复原并存；垂体４个月光镜下尚无变化，８个月开始出现窦样毛细管增生并扩张充血，嗜酸性细胞变大增多，呈现分化和功能活跃表现。     

GLYCOPROTEIN HORMONE ALPHA-SUBUNIT AND PROLACTIN RELEASE BY CULTURED PITUITARY ADENOMA CELLS FROM ACROMEGALIC PATIENTS: CORRELATION WITH GH RELEASE

In-vitro data of pituitary adenoma cells from 28 acromegalic patients were evaluated. In addition to GH, PRL was produced by 16 adenomas (57%) and alpha-subunit by 15 adenomas (54%) while there was a significantly higher incidence of tumours producing PRL and alpha-subunit simultaneously. From 26 pituitary adenomas enough cells were obtained in order to perform secretion studies. Percentage basal hormone release (medium: (medium + intracellular hormone)) x 100% of GH and alpha-subunit by 11 adenomas showed a close correlation while such a correlation for GH and PRL was present only in a subgroup of 10 of 13 adenomas. The responses of GH and alpha-subunit release to 10nM SMS201-995, 10nM bromocriptine, 100 nM TRH and 10nM GHRH were closely related in that a response or an absent response of GH release to the four secretagogues was virtually always attended with a response or an absent response respectively of alpha-subunit release. Such a relationship was less evident with respect to the effects of SMS201-995, bromocriptine. TRH and GHRH on GH and PRL release. We conclude that basal and secretagogue-induced alpha-subunit release by cultured pituitary adenoma cells from acromegalic patients closely follows the pattern of GH release while such a relationship for GH and PRL is present only in a subgroup of the adenomas secreting GH and PRL simultaneously.     

THE INFLUENCE OF BROMOCRIPTINE ON SERUM LEVELS OF GROWTH HORMONE AND OTHER PITUITARY HORMONES AND ITS METABOLIC EFFECTS IN ACTIVE ACROMEGALY

The effect of treatment with bromocriptine for 12--18 months on serum GH and metabolic responses was studied in sixteen patients with active acromegaly. Of this group ten patients showing a sustained GH reduction of more than 50% during an 8 h bromocriptine test, proved to be responsive to long-term therapy. In the responding patients GH levels decreased to 38% of the pretreatment level after 12 months of therapy. A dose higher than 10 mg did not produce a significantly greater effect. Prolactin and LH levels decreased in all patients, FSH levels showed a significant rise. Testosterone levels in the male patients increased significantly, indicating that the state of hypogonadism can at least be partially reversed. The GH levels became normal in only one patient. We conclude that the role of bromocriptine in acromagaly is limited and selective pituitary operation and/or irradiation is preferred as definitive treatment in most patients.     

EFFECT OF SUBACUTE CABERGOLINE TREATMENT ON PROLACTIN, THYROID STIMULATING HORMONE AND GROWTH HORMONE RESPONSE TO SIMULTANEOUS ADMINISTRATION OF THYROTROPHIN-RELEASING HORMONE AND GROWTH HORMONE-RELEASING HORMONE IN HYPERPROLACTINAEMIC WOMEN

It is known that dopaminergic neurotransmission is involved in the control of PRL, TSH and GH secretion. Cabergoline (CAB) is a new ergolinic derivative with a long-acting dopaminergic activity. We evaluated 11 women with pathological hyperprolactinaemia before and during sub-acute CAB treatment (0.8-1.2 mg/p.o.; 8 weeks). Simultaneous administration of TRH (200 micrograms i.v.) and GHRH 1-44 (50 micrograms i.v.) were carried out before and after 4, 8 and 10 week intervals from the beginning of CAB treatment. Basal PRL levels (2453.5 +/- S.E. 444.5 mU/l) were significantly reduced during CAB administration (week 4: 164.5 +/- 66.5 mU/l; week 8: 168.0 +/- 66.5 mU/l; P less than 0.01) and no variations were observed 2 weeks after drug discontinuation (week 10: 210.0 +/- 98.0 mU/l). PRL percentage change after TRH was increased by CAB (P less than 0.05). No variation in basal and TRH-stimulated TSH levels was found during CAB administration. A slight increase in GH basal levels (3.0 +/- 0.6 mU/l) was found after weeks 4 (6.4 +/- 2.0 mU/l) and 10 (5.8 +/- 1.6 mU/l) (P less than 0.05). GH response to GHRH was significantly enhanced (ANOVA: P less than 0.01) during sub-acute CAB treatment. A positive correlation was found between GH secretory area and weeks of CAB therapy (P less than 0.01). Our data show that CAB is very effective in lowering PRL secretion in hyperprolactinaemia, and is able to modify PRL and GH responses after TRH and GHRH. The increasing trend in GH basal and GHRH-stimulated GH levels seems to indicate that CAB can override the central dopaminergic tone which is operative in hyperprolactinaemia.     

SLEEP-WAKE PATTERNS AND INTEGRATED VALUES OF LUTEINIZING HORMONE, FOLLICLE STIMULATING HORMONE, PROLACTIN, GROWTH HORMONE AND THYROID STIMULATING HORMONE IN NORMAL AND CRYPTORCHID PUBERTAL PATIENTS

The sleep-wake behaviour of LH, FSH, PRI, GH and TSH was studied in seven cryptorchid patients (four unilateral and three bilateral cryptorchids) average age 12 years and in nine normal pubertal boys of 13 years (mean age). Blood samples were collected by a continuous withdrawal pump, every hour, for 24 h. The hormonal concentration for every fraction of time was measured and related to the sleep (Sc-), wake (Wc-) and total 24 h period (Dc-). The integrated concentrations of the corresponding periods (IS, IW, ID) were calculated as well as their ratios (IS/IW; IS/ID%). For GH and TSH, the data obtained demonstrated no differences between cryptorchid and pubertal subjects. The PRL secretion in cryptorchid patients was moderately increased during the hours of nocturnal sleep. A normal pubertal sleep-wake rhythm was found for gonadotrophins in both groups of subjects. More marked levels of LH secretion were observed in cryptorchid boys compared to normal pubertals. The presence of a sleep-wake rhythm was also found in the cryptorchid patients and normal pubertal subjects in the P 1 stage. These data suggest that the CNS "programme" which controls the onset of puberty may be normal in cryptorchid patients.     

THYROID HORMONE LEVELS AND PROTEIN BINDING IN PATIENTS ON LONG-TERM DIPHENYLHYDANTOIN TREATMENT

The effect of long-term diphenylhydantoin (DPH) treatment on thyroid hormone concentrations and protein binding was determined in a randomized controlled trial. As has been demonstrated previously, total thyroxine (T4) concentrations were significanly depressed in patients on DPH. There was no significant effect on indirect indices of protein binding of thyroid hormones, and the free thyroxine index (FTI) was also significantly depressed. Triiodothyronine (T3) and thyrotrophin (TSH) concentrations were either unaffected, or only very slightly affected by DPH. Significant effects on the FTI were still apparent 4 weeks after discontinuing treatment. It is concluded that the depression of total T4 levels observed in vivo is not due solely to diminished protein binding, but may instead be largely explained by reports suggesting enhanced degradation of T4 following DPH therapy. Since 1961 it has been known that diphenylhydantoin (DPH) has a significant effect on the levels of the circulating thyroid hormones in the plasma (Oppenheimer et al., 1961). It is known that the effect is extrathyroidal (Oppenheimer et al., 1961) and it was initially assumed to be due to an effect on protein binding. This assumption followed the demonstration that DPH decreased the binding of thyroxine (T4) to throxine binding globulin (TBG) in vitro (Oppenheimer & Tavernetti, 1962). However, more recent work (Chin & Schussler, 1968; Larsen et al., 1970; Hansen et al., 1974; Stjernholm et al., 1975) has suggested that there may be a true depression of free T4. Most previous studies have been in epileptic patients for whom the control groups were not totally comparable (Hansen et al., 1974; Chin & Schussler, 1968) or in normal subjects who underwent DPH therapy for only a short time (i.e. 1-2 weeks, Hansen et al., 1974). Moreover, DPH dosage in earlier studies has for the most part been arbitrarily decided upon, or evaluated by clinical signs. It is known that there are extremely variable individual responses to given doses of DPH (Richens & Dunlop, 1975), resulting in variable plasma levels of DPH. This study describes the effects of long-term DPH treatment on thyroid function and thyroid hormone protein binding. A comparable control group was also studied, and DPH concentration in the blood was continually monitored. The same patients were reexamined after discontinuation of therapy, to elucidate the duration of the effect.     

甲状腺激素对左室心肌弛张功能的影响及其可能机制

本文用心脏超声及放射免疫法分别检测２０例甲状腺功能亢进症（甲亢）患者予抗甲状腺素治疗前后之心脏弛张功能（ＩＩａ－ＭＶＯ、ｍａｘＲＦＶ、ＰｅａｋＥ、ＰｅａｋＡ、Ｅ／Ａ）、心脏前与后负荷（ＬＶＥＤＶ、ＥＳＳ）、左室收缩力（ＥＳＳ／ＬＶＥＳＶ）及血清Ｔ３和血浆环磷酸腺苷（ｃＡＭＰ）。结果显示：治疗前甲亢组与对照组比较，ＩＩａ－ＭＶＯ明显缩短、ｍａｘＲＦＶ、ＰｅａｋＥ、ＰｅａｋＡ明显增高。甲亢组血浆ｃＡＭＰ、Ｉｌａ－ＭＶＯ、ｍａｘＲＦＶ、ＰｅａｋＥ和Ｅ／Ａ与血清Ｔ３水平有显著的简单相关。血浆ｃＡＭＰ、ＩＩａ－ＭＶＯ、ｍａｘＲＦＶ和ＰｅａｋＥ与Ｔ３有显著偏相关，但ＰｅａｋＥ与Ｔ３之偏相关系数小于年龄及前负荷与Ｔ３之偏相关系数。甲亢组经平均１８０天抗甲状腺素治疗后，其左室舒张功能、血浆ｃＡＭＰ与治疗前比较有显著差异，而与对照组无差异。