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In order to throw light upon the eventual need for iodine supplementation in Denmark, four age groups of women (15, 30, 45 and 60 years) from the Holbaek municipality were invited for a clinical and ultrasound study of thyroid volume, structure and function. Of the 570 women invited, 391 accepted and were divided into the following groups: group I: 15 years, N = 113; group II: 30 years, N = 100; group III: 45 years, N = 98; group IV: 60 years, N = 80. The results were as follows the thyroid gland was palpable in 39% and visible in 16% of the entire group; 19% had a family history of thyroid disorders and 7.6% had a previous thyroid disorder. Thyroid volumes (median (range)) as measured by ultrasound were 12 ml (4-29 ml), 18 ml (5-47 ml), 18 ml (7-64 ml) and 18 ml (9-51 ml) in groups I-IV, respectively. The calculated 24-h iodine excretion was 65 micrograms (19-365 micrograms), 88 micrograms (15-274 micrograms), 97 micrograms (40-737 micrograms) and 83 micrograms (50-999 micrograms) in groups I-IV, respectively. An abnormal echo structure was present in 3, 10, 21 and 30%, respectively. Defining a goitre as a thyroid volume above 28 ml indicated a goitre prevalence of 17% in females aged 30-60 years in the Holbaek area of Denmark. Among the 60-year-old women, 3% had a clinically significant goitre (WHO grade III). Thyroid volume did not correlate with iodine excretion. The benefit of iodine supplementation is discussed.

In order to detect somatic and psychomotor disturbances in children and adolescents residing in areas of iodine deficiency, schoolchildren from three areas with different degrees of iodine deficiency were studied. In Randan, the prevalence of severe endemic goiter was accompanied by alteration in thyroid function, increased thyrotropin levels and retardation of both bone and psychomotor age and decreased intellectual quotient. In Tehran, where iodine deficiency is mild, visible goiter was present in 15% of schoolchildren but no alterations in thyroid function, serum thyrotropin, somatic or psychomotor development could be detected. In Zagoon, where the prevalence and severity of goiter was less than Randan but more than Tehran, thyroid function was normal but slightly decreased as compared to Tehran; somatic development was unaltered, but retardation in psychomotor development was evident and the mean intellectual quotient was less than that of Tehranian schoolchildren. These findings indicate the occurrence of physical and psychomotor disturbances in apparently normal schoolchildren from areas of iodine deficiency. Alteration in psychomotor development may occur in children with normal physical growth, due to iodine deficiency.

A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His decreased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth factor I concentrations were elevated, with levels between 10 and 20 micrograms/l and 4.4 and 7.3 kU/l, respectively. In spite of hyperthyroidism (free thyroxine, 45 pmol/l; free triiodothyronine, 24 pmol/l), plasma thyrotrophin remained at 2.8 mU/l without any response to thyrotrophin-releasing hormone and could not be suppressed with exogenous administration of triiodothyronine. Plasma alpha-subunits were raised to 3.3-3.7 U/l (normal 0.4-1.1 U/l). Pathological examination of the surgically removed tumour showed a pituitary adenoma with the immunohistochemical presence of growth hormone, thyrotrophin, prolactin and alpha-subunit. This is the first report of a growth hormone-, thyrotrophin- and alpha-subunit-producing pituitary adenoma, which occurred in a familial setting.

Similar features during chronic amiodarone treatment and hypothyroidism suggest that amiodarone induces a state of "triiodothyronine (T3)-resistance" or "cardiac hypothyroidism", which may predispose the heart to pump failure under conditions with severe strain, such as recovery after cardiac surgery. Disagreements exists as to how amiodarone, and possibly its main metabolite desethylamiodarone, act upon the various receptor systems in the heart. The aim of the present study was to elucidate whether chronic amiodarone treatment leads to a functional reduction in the number of myocardial nuclear T3 receptors, the myocardial tissue T3 concentration and the number of beta-receptors and voltage-operated Ca(2+)-channels. Finally, special attention was drawn to any changes that could contribute to explain previous reports on reduced haemodynamic reserve in animals exposed to severe cardiac strain, such as cardiac surgery. Pigs (72 +/- 2 kg) were assigned randomly to amiodarone treatment (20 mg.kg-1.day-1 for 30 +/- 1 days, N = 8); controls received no medical treatment (N = 6). The left ventricle was evaluated for beta-adrenergic receptors, voltage-operated Ca(2+)-channels, T3 nuclear receptors and tissue T3 concentration. Maximum binding capacity for beta-receptors and Ca(2+)-channels was reduced in amiodarone-treated pigs (by 38%, p < 0.05, and by 52%, p < 0.01) and correlated with tissue drug concentrations for both receptor types (p < 0.05). No changes were observed concerning nuclear T3 receptors. In vitro competition studies revealed that amiodarone, but not desethylamiodarone, possessed binding properties to Ca(2+)-channels, whereas neither of the compounds bound to beta-receptors. Desethylamiodarone, but not amiodarone, competitively inhibited T3 binding to its nuclear receptors. Myocardial T3 was undetectable (< 0.05 nmol/kg wet wt) in amiodarone-treated pigs. From our observations we suggest that the active metabolite desethylamiodarone, rather than the parent drug, is mainly responsible for the observed local hypothyroid-like effects during amiodarone treatment. The observed changes after treatment with low-dose amiodarone in pigs are likely to have biological implications. Functionally, the changes may imply reduced cardiac reserve during conditions of extraordinary strain.

Forty-nine children who had undergone treatment with cyclophosphamide and total body irradiation before bone marrow transplantation were investigated for impaired endocrine function. Twenty-six patients received single fraction total body irradiation as a dose of 9-10 Gy, whereas 23 patients received fractionated total body irradiation as a total dose of either 12 Gy divided into six fractions or 14.4 Gy divided into eight fractions, administered over 3 or 4 days. Half of the patients in the single fraction group and nine in the fractionated group had received cranial irradiation prior to total body irradiation. Pathological changes in thyroid function were observed in 19 patients (73%) of the single fraction group (elevated thyrotrophin (58%) and decreased thyroxine levels (15%)), whereas in the fractionated group only six patients (25%) developed transient raised thyrotrophin levels: the mean observation period was 3.2 years in the single fraction group and 2.7 years in the fractionated group. The stimulated growth hormone peak concentration was influenced significantly by previous cranial irradiation and was independent of the type of total body irradiation administered. In the patients who had received cranial irradiation, the mean growth hormone peak levels were 8.4 mU/l (single fraction group) and 13.9 mU/l (fractionated group), whereas in those who received only total body irradiation they were 24.9 mU/l(single fraction group) and 28.1 mU/l (fractionated group). The basal gonadotrophin concentration in children older than 9 years showed elevated levels in nine patients (50%) of the single fraction group and in only three patients (30%) of the fractionated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Lymphocytic hypophysitis usually occurs in the antepartum or postpartum period and recovery of pituitary dysfunction has not been documented in most cases reported previously. We present a 50-year-old woman with lymphocytic hypophysitis who spontaneously recovered from panhypopituitarism over 18 months with the disappearance of an intrasellar mass. Although lymphocytic hypophysitis is thought to be an autoimmune disease, the clinical and pathogenetic significance of circulating antipituitary autoantibodies has not been clarified. Antipituitary antibodies were studied by immunofluorescence in blood samples obtained during the whole clinical course in this particular patient. Antibodies against rat pituitary cytosol were positive during the period of hypopituitarism and became negative when pituitary function recovered. Antibodies reacting with intact prolactin-secreting rat GH3 and corticotropin-secreting mouse AtT-20 cells were also positive during her period of hypopituitarism. They remained positive for several years after the recovery of pituitary function. We conclude that circulating antibodies against rat pituitary cytosol are good markers of pituitary inflammation in this patient. The other point to be emphasized in this case is the simultaneous development of painless thyroiditis and lymphocytic hypophysitis. We have discussed the pathogenic relationship of these two diseases on the basis of similar cases reported previously.

Until now, most potent inhibitors of monodeiodination are iodinated, propylthiouracil being an exception. We report here studies on a new non-iodinated substance, triethylene glycol bis-3-(3-tert-butyl-4-hydroxy-5-methyl-phenyl) propionate (TK 12627 or Irganox), which is used as a very efficient antioxidant in the chemistry of plastics. The studies were performed with 23 hypothyroid rats that received Irganox in their daily food (8 mg.day-1 x (100 g body wt)-1) for 3 weeks. Thyroxine (T4) metabolism was studied by implanting minipumps delivering 2.3 nmol T4.day-1 x (100 g body wt)-1 for 1 week. On day 1 before sacrifice, another minipump containing [125I]-3,5,3'-triiodothyronine (T3, 2.6 microCi/day) and [131I]-3,3',5'-triiodothyronine (rT3, 2.1 microCi/day) was implanted. The results showed that with Irganox treatment serum T4 concentrations were higher (p < 0.05). Serum T3 concentrations markedly decreased (1.07 +/- 0.07 vs 0.65 +/- 0.04 nmol/l), accompanied by a decrease of free T3 concentrations (p < 0.001). Serum rT3 concentrations increased by 50% (p < 0.001). Serum thyrotropin levels were mostly unmeasurable. The plasma clearance rate decreased slightly for T4 (19%, p < 0.05) and remarkably for rT3 (46.7%, p < 0.001). The conversion rate of T4 to rT3 did not change. Deiodinase type I (5'D-I) activity decreased in both liver and kidney tissues by 54% and 52%, respectively, and correlated with T3 (r2 = 0.79 and 0.65, respectively). Brain deiodinase type III (5D-III) was unchanged and type II (5'D-II) was unmeasurable.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of recombinant GH on strength, body composition and endocrine parameters in power athletes was investigated in a controlled study. Twenty-two healthy, non-obese males (age 23.4 +/- 0.5 years; ideal body weight 122 +/- 3.1%, body fat 10.1 +/- 1.0%; mean +/- SEM) were included. Probands were assigned in a double-blind manner to either GH treatment (0.09U (kg BW)-1 day-1 sc) or placebo for a period of six weeks. To exclude concurrent treatment with androgenic-anabolic steroids urine specimens were tested at regular intervals for these substances. Serum was assayed for GH, IGF-I, IGF-binding proteins, insulin and thyroxine before the onset of the study and at two-weekly intervals thereafter. Maximal voluntary strength of the biceps and quadriceps muscles was measured on a strength training apparatus. Fat mass and lean body mass were derived from measurements of skinfolds at ten sites with a caliper. For final evaluation only data of those 8 and 10 subjects in the two groups who completed the study were analyzed. GH, IGF-I and IGF-binding protein were in the normal range before therapy and increased significantly in the GH-treated group. Fasting insulin concentrations increased insignificantly and thyroxine levels decreased significantly in the GH-treated probands. There was no effect of GH treatment on maximal strength during concentric contraction of the biceps and quadriceps muscles. Body weight and body fat were not changed significantly during treatment. We conclude that the anabolic, lipolytic effect of GH therapy in adults depends on the degree of fat mass and GH deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

We measured changes in serum insulin-like growth factor-1 (IGF-1), calcitriol, parathyroid hormone (PTH), thyroid hormones, insulin, and plasma glucagon in response to seven days of treatment with a pharmacological dosage of recombinant human growth hormone (r-hGH) (0.1 IU/kg sc twice daily) or placebo in 20 normal male volunteers to evaluate whether the effect of r-hGH on biochemical bone markers could be attributed to changes in these hormones. Serum IGF-1 (p < 0.001) and vitamin D-binding protein (p < 0.001) increased steadily during treatment returning to baseline at day 14. Total calcitriol (p < 0.01) and free calcitriol index (p < 0.001) increased transiently at day 4. Furthermore, serum insulin (p < 0.001) and both total (p < 0.001) and free triiodothyronine (p < 0.02) increased during treatment, while serum PTH and plasma glucagon remained unchanged. In conclusion, pharmacological doses of r-hGH increased not only IGF-1 but also free-calcitriol index, insulin, and free T3. The increase in these hormones may be co-responsible for some of the observed effects of r-hGH on bone turnover and calcium homeostasis.

Circulating levels of T3, T4, gamma-amino-butyric acid, glutamate, 5-hydroxytryptamine, histamine, monoamine oxidase and histaminase were studied in 45 (25M, 20F) hyperthyroid patients and 46 (25M, 21F) normal healthy volunteers. Increased levels of blood 5-hydroxytryptamine, histamine and glutamic acid were observed along with elevated T3 and T4, whereas plasma gamma-aminobutyric acid, monoamine oxidase and histaminase activities were found to be low in both male and female patients. After three months of treatment, circulating levels of 5-hydroxytryptamine, histamine and glutamic acid decreased significantly along with normalization of thyroid hormones and with an increase in the concentrations of gamma-aminobutyric acid, monoamine oxidase and histaminase. There was a positive correlation between these amines and thyroid hormone levels. The findings thus suggest that alterations in the metabolism of biogenic amines may be related to an altered metabolism in thyrotoxicosis, and these parameters may prove to be useful markers for diagnosis and follow-up of these patients.

We have evaluated the efficacy of high-dose intravenous immunoglobulin treatment in Graves' ophthalmopathy, and have carried out a prospective randomized clinical trial, including a single-blind evaluation, whereby 14 patients were assigned to two different treatment groups: 7 patients were treated with intravenous immunoglobulin and orbital radiotherapy (Group 1) and 7 patients were given intravenous immunoglobulin alone (Group 2). The results of the intravenous immunoglobulin treatment were also compared with those obtained in a Historical Control Group (12 patients) treated with systemic methylprednisolone and orbital irradiation. Degree of ocular involvement and response to treatment were assessed by ophthalmopathy index. The mean initial and final ophthalmopathy index showed no significant difference among the three groups. Comparison between the mean initial and final ophthalmopathy index showed a statistically significant reduction (p less than 0.005) in all three groups, the observed changes being confirmed by orbital computerized tomography in Groups 1 and 2. Corticosteroid treatment was associated with major and minor side effects, while no important adverse reactions were observed during intravenous immunoglobulin treatment. Even considering our results as preliminary, we conclude that intravenous immunoglobulin treatment is effective and safe in improving Graves' ophthalmopathy.

Aging in rats is characterized by low plasma concentrations of thyroid hormones with unchanged levels of TSH, suggesting an altered TSH action in addition to the impaired regulation of TSH secretion. To evaluate TSH action we determined TSH binding to thyroid membranes of young and old male rats (3-4 and 24-26 months of age), as well as the activity of adenylate cyclase in basal and stimulated conditions. Saturation analyses of [125I]-bTSH to thyroid membranes in the presence of increasing quantities of unlabelled bTSH (0.03-100 mU) show two types of binding sites, one of high affinity (Ka 1.5 10(9) mol l-1) the other of lower affinity (Ka 1.2 10(8) mol l-1), which are similar in both age groups. The number of TSH binding sites of high affinity is less in old rats than in young rats (7.6 +/- 0.9 vs 14.8 +/- 1.1 TSH mU/mg protein, N = 11 and 10 respectively, p less than 0.001), whereas the number of binding sites of low affinity is not significantly different (76.0 +/- 8.2 vs 99.1 +/- 9.0 TSH mU/mg protein). The activity of adenylate cyclase determined in basal conditions is similar in both old and young rats (1.11 +/- 0.12 vs 1.04 +/- 0.9 nmol cAMP/2 h x mg/protein). TSH (10 mU) induced a significant increase in cAMP formation with the thyroid membranes from young rats but not with those from old rats. In contrast, the stimulation of cAMP formation by GTP (2 mmol/l) or forskolin (10 mmol/l), two direct stimulators of adenylate cyclase, is similar in both groups of rats (200% and 250%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of amiodarone on thyroid hormone metabolism in heart, muscle, liver and kidney was investigated. Rats were treated ip with a high (100 mg.kg-1.day-1) or a low (50 mg.kg-1.day-1) dose of amiodarone for 10 days. Serum T3 was dose-dependently depressed (mean 30 and 54% of controls, respectively, p less than 0.01). rT3 was elevated (to 663 and 313% of controls, p less than 0.01 and 0.05, respectively). Serum T4 was depressed only in the high-dose group (to mean 80%, p less than 0.05). Tissue concentrations of T3 in the heart and muscle from treated animals did not differ from controls, whereas liver and kidney T3 contents were markedly reduced in both groups (p less than 0.05). Heart T4 and rT3 were elevated to about 200% of controls (p less than 0.01 and 0.05, respectively). The same pattern was observed in the other tissues. Iodothyronine-5'-monodeiodinase activity was significantly depressed in all tissues; heart: 32 and 28% of controls (p less than 0.05); muscle: 36 and 49% (p less than 0.01); liver: 11 and 13% (p less than 0.01); kidney: 22 and 28% (p less than 0.01), respectively. In conclusion, amiodarone depresses iodothyronine-5'-monodeiodinase activity in the heart, muscle, liver and kidney in a dose-dependent manner, resulting in lowered T3 concentrations in the liver and kidney, whereas no reduction of tissue T3 content is observed in the heart and muscle. This may indicate that T3 from plasma may cross the cardiac sarcolemma without hindrance.

Thirty-five pregnant women with thyroid antibodies were followed during pregnancy and 12 month post partum. Twenty antibody-negative women served as controls and none of these developed postpartum thyroiditis in contrast to 12 of 35 antibody-positive women. Umbilical cord blood was collected at birth for measurements of thyroid antibodies, and blood samples for measurements of thyroid hormones were obtained at 5 and 30 days of age in the infants together with a clinical examination. There were no differences between the infants of antibody-positive and -negative mothers or the infants of those who developed postpartum thyroiditis with regard to gestational age at birth, birth weight, birth length or Apgar score, and no difference in thyroid function of the mothers and infants. However, serum TSH level was significantly higher in mothers who subsequently developed postpartum thyroiditis. Furthermore, a significantly lower growth during the first 30 days of life was observed in their infants. Our observations suggest a relationship between the maternal thyroid status in pregnancy and early growth in infancy.

The effects of chronic (40%) food restriction from 6 weeks of age were studied in 28-month-old male Fischer-344 rats; the results were compared with ad libitum-fed, old and young male rats at 28 and 3 months of age, respectively. Pituitary luteinizing hormone was similar in all old rats and was significantly lower than in young rats. In old ad libitum-fed, but not in food-restricted rats, serum levels of LH, testosterone and T4 were significantly lower than in young rats. Serum levels of T3 did not differ between young and old rats. Type-II 5'-deiodinase activity in brown adipose tissue was similar in both groups of old animals and was significantly depressed as compared with that in young rats. Serum levels of triglycerides were significantly depressed in food-restricted rats, but were significantly increased in ad libitum-fed rats as compared with young rats. Both groups of old rats had significantly elevated serum levels of cholesterol over that in young rats, but the level was significantly lower in food-restricted as compared to ad libitum-fed animals. The results are consistent with the notion that life-long food restriction tends to preserve the activity of many metabolic functions.

Calcitonin has an uncertain role in the preservation of bone mass. Since surgical thyroidectomy abolishes the calcitonin secretion in response to calcium, the bone mineral density at the radius shaft and lumbar spine was measured in 60 patients (5 men, 16 premenopausal, 34 postmenopausal euparathyroid and 5 postmenopausal hypoparathyroid women) who had undergone near total thyroidectomy for thyroid cancer 8.4 +/- 0.7 years before the study. All patients were maintained on suppressive doses of thyroid hormones. Bone mineral density values of the radius shaft (expressed as Z-score) of 34 postmenopausal euparathyroid women was significantly below the normal average (mean +/- SEM = -0.59 +/- 0.2; p = 0.01). Bone mineral density of the lumbar spine was also below the normal average although the difference only approached statistical significance (-0.36 +/- 0.2; 0.05 less than p less than 0.1). The bone mineral density of neither the radius nor the spine differed from normal levels in the premenopausal women and the postmenopausal hypoparathyroid women. Unexpectedly, the bone mineral density of the spine was significantly increased in the 5 thyroidectomized men. The results indicate that thyroidectomized women have a diminished bone mass after the menopause only if parathyroid function is normal. Since the patients were receiving thyroid hormone at suppressive doses, the present study is not able to separate the relative contributions of calcitonin deficit and exogenous thyroid on bone mass loss.

We evaluated serum thyroid hormone and thyroid antibody levels, the serum TSH response to TRH, and the circadian pattern of serum TSH in 10 children and adolescents after radiation therapy for acute lymphoblastic leukemia. Four patients had received central nervous system preventive cranial irradiation and intrathecal chemotherapy, and the remaining 6 patients were treated with craniospinal irradiation for central nervous system relapse. Serum total T4 and T3 concentrations were within the normal range and thyroid antibodies were negative in all patients. Four patients who had received craniospinal irradiation had low free T4 levels. Prior to TRH administration, the overall mean serum TSH concentration was 5.4 +/- 1.3 mU/l, and the mean peak response to TRH was 33 +/- 6.5 mU/l. Both were significantly increased when compared to the levels observed in our control population (p less than 0.05 and less than 0.025, respectively). The overall mean nadir diurnal TSH was 3.6 +/- 0.8 mU/l, and the mean peak nocturnal TSH was 6.9 +/- 1.3 mU/l, both significantly elevated when compared to normal children (p less than 0.025). The mean nocturnal TSH surge, however, was not significantly different from normal. Four of 6 children treated with craniospinal irradiation, and one of four children treated with cranial irradiation had increased basal and peak serum TSH concentrations in response to TRH. One of the patients treated with cranial irradiation had an abnormal nocturnal TSH surge. We conclude that subtle primary hypothyroidism is relatively common in patients with acute lymphoblastic leukemia, particularly in those who have been treated with craniospinal irradiation.

We used microcalorimetry to measure lymphocyte heat production rate in patients with clinical and laboratory hyperthyroidism (serum TSH decreases, serum FT4 increases, serum FT3 increases), subclinical hyperthyroidism (serum TSH decreases, serum FT1 increases, serum FT3 =), and subclinical hypothyroidism (serum TSH increases, serum FT4 decreases, serum FT3 =) compared with healthy controls (N = 13). The lymphocyte heat production rate was significantly correlated to the free thyroxine level (r = 0.53, p less than 0.01) and to the free triiodothyronine level (r = 0.51, p less than 0.01) when calculated from pooled data for the three patients groups. The hyperthyroid patients (N = 8) had a significantly increased lymphocyte heat production rate, 3.43 +/- 0.25 pW/cell, as compared with 2.31 +/- 0.12 pW/cell in the control group (p less than 0.001). The groups with subclinical hyperthyroidism (N = 7) and subclinical hypothyroidism (N = 9) had lymphocyte heat production rates of 2.14 +/- 0.11 and 2.56 +/- 0.15 pW/cell, respectively, not significantly different from that in the controls. Consistently, there was no significant difference between patients with subclinical hyperthyroidism (N = 5) and controls (N = 5) with regard to lymphocyte energy production as calculated from separately measured oxygen consumption rates in vitro, 1.36 +/- 0.20 and 1.56 +/- 0.12 pW/cell, respectively. Thus microcalorimetry seems to be suitable for studying the influence of thyroid hormones on cellular metabolism. Subclinical thyroid dysfunction does not seem to alter the overall rate of lymphocyte metabolism.

The sex-related differences observed in the regulation of TSH secretion was further investigated by determination of the densities of T3 nuclear and TRH membrane receptors as well as the activity of 5'-deiodinase (5'D) in the anterior pituitary gland of adult male and female rats. The respective modulatory roles of androgens and estrogens on these parameters were evaluated by similar determinations carried out in castrated and in estrogen-treated male rats. The density of pituitary T3 and TRH receptors and the activity of 5'D type II were significantly greater in the female than in the male rats. The E2-treated male rats disclosed a female profile, viz. also greater densities of T3 and TRH receptors when compared with control male rats (2.3 +/- 0.2 vs 1.8 +/- 0.2 fmol T3/mg gland and 9.4 +/- 0.8 vs 6.0 +/- 0.8 fmol TRH/mg gland, mean +/- SEM), whereas no changes were found in the castrated rats. The E2-treated rats and the castrated rats exhibited an increased pituitary activity of 5'D, type II (0.87 +/- 0.10 and 0.66 +/- 0.05, respectively, vs control 0.34 +/- 0.07 pmol rT3.h-1.(mg protein)-1), suggestive of a stimulatory effect of E2 and of an inhibitory effect of androgens on this parameter. In contrast, no differences in hepatic 5'D were found between all groups, illustrating the well-known tissue-specific regulation of 5'D. These results demonstrate that the sex difference in the density of pituitary T3 and TRH receptors and the activity of 5'D in the adult rat is mainly due to a modulatory effect of estrogens, which may be responsible for the sex-dependent regulation of TSH secretion.

Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 micrograms TRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life.

The prognosis of atrophic hypothyroidism with blocking type TSH-binding inhibitor immunoglobulin was studied. Among 45 patients (16 males and 29 females) with overt hypothyroidism (serum TSH greater than 40 mU/l) without goitre, thyroid autoantibody to microsomal antigen was positive in 38 or 84.4%, and 4 or 8.9% had TSH-binding inhibitor immunoglobulin, which was shown to be a TSH-stimulation blocking antibody by cAMP production assay using cultured porcine thyroid cells. Thyroidal radioactive iodine uptake was low and thyroid hormone replacement therapy was required. Long-term follow up of 2 patients with strongly positive TSH-binding inhibitor immunoglobulin for 2 to 7 years, however, revealed recovery of the thyroid function after steroid therapy or spontaneously with iodide restriction, respectively, correlating with decrease in both TSH-binding inhibitor immunoglobulin and TSH-stimulation blocking antibody activities. Thyroidal radioactive iodine uptake became normal and histological examination of the thyroid in one patient revealed well-preserved thyroid follicles with lymphocytic infiltration. Recovery of thyroid function can be expected with a decrease in TSH-binding inhibitor immunoglobulin activity in atrophic hypothyroidism, which is not necessarily the end stage of chronic thyroiditis.

Triiodothyronine (T3) binding to Ficoll-Isopaque purified human lymphocytes was studied. During incubation of lymphocytes with [125I]T3 in a calcium-free medium at 37 degrees C, maximal uptake of T3 in nuclei occurrred after 2 h and declined after prolonged incubationd incubation . Incubation of lymphocytes with T3 concentrations ranging from 1 X 10(-11) TO 1 X 10(-9) mol/l and subsequent treatment with Triton X-100 to strip off [125I]T3 bound with low affinity was used for the estimation of affinity and capacity of nuclear T3 binding sites. The mean equilibrium affinity constant (Ka) estimated with the Scatchard method in 11 euthyroid healthy subjects was 4.5 X 10(9) l/mol, and the mean maximal binding capacity 25 X 10(-5) mol/100 mug DNA. In a female patient with peripheral resistance to thyroid hormone action, the estimated Ka was 3.5 X 10(9) l/mol and the number of T3 binding sites 37 X 10(-15) mol/100 mug DNA. Although not statistically different from the mean value in euthyroid subjects, this Ka value was outside the range of control values observed and was considered presumptive evidence that the nuclear T3 receptors in this patient have abnormally low affinity for its ligand. The nuclear T3 binding capacity in this patient was significantly increased.

Basal plasma concentrations of Prl, LH, FSH, GH, TSH, T3, T4, resin T3 uptake ( RT3U ), and oestradiol as well as hormone responses to iv metoclopramide (MTC) were investigated in 16 consecutive patients with normoprolactinaemic, normogonadotrophic amenorrhoea. The control group consisted of 17 normal menstruating women between day 3 and 6 of the menstrual cycle. The mean age of the amenorrhoeic patients was 24.0 years (range 19 to 34) and the mean duration of amenorrhoea was 31 months (range 12 to 60). Amenorrhoeic patients had significantly (P less than 0.05) lower basal levels of LH, oestradiol and RT3U , whereas other hormone levels were similar in the two groups. Plasma Prl and TSH concentrations rose significantly (P less than 0.05) after the administration of MTC in the two groups. A significant positive correlation (r = 0.69 P less than 0.01) was found between the TSH response to MTC and basal TSH levels in controls, but not in amenorrhoeic patients. Plasma LH levels increased significantly (P less than 0.05) in amenorrhoeic patients, but not in controls. The Prl and TSH responses to MTC were significantly (P less than 0.001) lower in amenorrhoeic patients than in normal women. In amenorrhoeic patients none of the hormonal parameters correlated significantly (P greater than 0.05) with the percentage of ideal body weight. It is concluded that the hormonal changes in amenorrhoeic patients may in part be caused by a raised dopaminergic activity leading to a depression of central ovulatory mechanisms.

Endemic goitre of moderate severity was mainly found in the east of Finland in the 1930's. Studies in the 1950's showed an average daily iodine intake of 65-70 micrograms in the west and 50-65 micrograms in the east of the country. The use of iodized salt was introduced in the late 1940's but added only 15 micrograms of iodine to the daily intake. In the late 1950's iodine prophylaxis was intensified and the use of salt containing 25 mg KI/kg was recommended. In 1978 about 95% of all household salt used in the Savonlinna area was iodized. This region in the east of Finland has been used as an area of surveillance and studies have been carried out there in 1959, 1969 and 1979. During this period the thyroidal uptake decreased from 67 to 23% in non-goitrous subjects and from 62 to 28% in goitre patients the difference between the two last figures being statistically significant. The goitre patients also had significantly higher serum thyroxine and triiodothyronine levels. During the same period the urinary excretion of stable 127I increased from 45 micrograms to about 250 micrograms a day. Concomitantly the goitre prevalence among school children has decreased. Having been in the early 1950's in most parts 15-30% it is generally now 1-4%. It seems that the iodine intake is now adequate and that the endemia is gradually subsiding.

Thyroidal binding of iodide was studied by kinetic analysis of [123I]iodide uptake and its discharge by perchlorate in 80 hyperthyroid subjects receiving antithyroid drug therapy. Five dosage regimens ranging from 5 mg carbimazole twice daily to 15 mg methimazole twice daily were studied. Binding inhibition was estimated at 5-7 h after drug as an index of the mean effect of the 12 hourly regimen. In all cases, except one in the lowest dose group, binding was found to be markedly reduced with mean binding rates ranging from 0.002 to 0.020 min-1 (normal greater than 0.15 min-1). The net clearance of iodide in the lowest dose group was reduced to a mean value near the upper limit of the euthyroid range, whereas in the highest dose group it lay at the lower limit of the euthyroid range. These results were reflected in the serum thyroid hormone response. There was a reducing incidence of inadequate control of hyperthyroidism and an increasing incidence of hypothyroidism with increasing thiourylene dose. The exit rate constant of free iodide for the various doses showed values from 0.048 to 0.055 min-1. Corresponding mean values for the discharge rate constant after perchlorate were 0.087 to 0.105 min-1. This suggests that perchlorate increases the rate of iodide release from the thyroid gland. Studies at a later interval after drug (12-14 h) showed no change in discharge rate constant. This leads to the conclusion that perchlorate may further inhibit iodide binding in subjects receiving antithyroid drug therapy.

Inappropriate hypersecretion of TSH was investigated in a 25 year old man whose hyperthyroidism had relapsed 4 years after subtotal thyroidectomy. Serum TSH levels were further increased by both TRH and metoclopramide and were partially suppressed by triiodothyronine (120 micrograms/day). The serum alpha-subunit: TSH molar ratio was less than 1.0, and computerised axial tomography showed no evidence of a pituitary tumour. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. A long-acting somatostatin analogue (SMS 201-995), 50 micrograms injected sc twice-daily for three days, suppressed TSH levels and nearly normalised thyroid hormone levels. Somatostatin analogues may be therapeutically useful in thyrotoxicosis due to non-tumoural inappropriate TSH hypersecretion.

We previously reported increased mean serum 1,25-dihydroxyvitamin D (1,25-(OH)2D) and increased trabecular bone remodelling in patients with medullary thyroid carcinoma (MCT) and hypercalcitoninaemia. In the present paper we report that serum 1,25-(OH)2D and trabecular bone remodelling decreased following surgical cure for MCT and hypercalcitoninaemia in 4 patients despite no detectable post-surgical hypoparathyroidism or hypothyroidism. The results obtained in the present small number of patients suggest that the altered vitamin D metabolism and trabecular bone remodelling in patients with MCT is caused by the hypercalcitoninaemia.

The incidence of malformation is increased in infants of hyperthyroid or hypothyroid woman. Although many papers reported that the fetus is insulted from maternal thyroid hormone, the placenta (maternal-fetal barrier) is not yet fully developed before 11.5 days of gestation in rat embryos, suggesting the effect of thyroid hormone on early rat embryogenesis. This study was, therefore, undertaken to investigate whether excess or lack of thyroid hormones would affect early embryogenesis in rat embryo culture. Malformations including open neuropore and microencephaly were observed in 10 of 30 embryos incubated in hyperthyroid serum, and in 12 of 42 cultured in T3-enriched normal serum. Similar malformations were observed on 14 of 42 embryos cultured in hypothyroid serum and in 10 of 30 cultured in hypothyroid serum supplemented with T3. The frequencies of these malformations were significantly higher than in the control embryos (0 in 72 embryos) cultured with normal rat serum. These results suggest that the maternal thyroid status might play an important role for the complication of fetal malformations during early gestational period.

Endemic goitre and cretinism are still a public health problem in China. An epidemiological survey showed that about 5% of the inhabitants in Daxin village, Henan province, had goitre or cretinism after an iodized salt prevention programme had been carried out for two decades. The main food for the inhabitants of this area has an iodine content less than 30 nmol/kg and the water for cooking and drinking has an iodine concentration between 7-12 nmol/l. We studied thyroid function in subjects of this village. There were 42 with grade 0 goitre (males 29, females 13), 42 grade I (males 23, females 19), 27 grade II (males 9, females 18), 31 grade III (males 14, females 17) and 34 cretinism patients (males 30, females 4) diagnosed and classified according to WHO criteria. Serum T4, free T4, T3, free T3, T3 uptake, TSH and thyroglobulin were measured in these subjects. The patients with goitre or cretinism had significantly decreased serum free T4 and increased serum T3 and free T3 levels compared with those of controls. Thyroid size was positively correlated with age and serum thyroglobulin concentrations. Serum thyroglobulin was significantly increased even in the grade 0 goitre subjects. The percentages of subjects with serum free T4 less than 12 nmol/l, T3 greater than 2.5 nmol/l, free T3 greater than 5.2 pmol/l, TSH greater than 3.5 mU/l, T3/T4 ratio greater than 0.03 and free T3/free T4 ratio greater than 0.36 were significantly higher among goitre and cretinism patients than among controls. The data suggest that there is partial compensation for a marginal deficiency of iodine in the inhabitants of this village.

Nine consecutive patients with unilateral ophthalmopathy with suspected endocrine pathogenesis were investigated with a TRH test, a T3 suppression-test, thyroid autoantibodies and a subsequent computerized tomography (CT)-scan. All patients were clinically and biochemically euthyroid. Seven of 9 patients had a normal TRH test and 6 of 7 had a normal T3 suppression test. Slightly to moderately elevated microsomal and thyroglobulin (determined with radioimmunoassay) autoantibodies were found in 5 of 8 patients and in 1 patient thyroid stimulating immunoglobulins (TSI) were found. Three of the patients had normal thyroid function tests and no detectable thyroid autoantibodies. The subsequent CT-scan revealed that one of these had a maxillary tumour protruding into the orbita. The remaining 8 patients had enlargement of one (3 patients) or more (5 patients) eye muscles. Two of the 8 patients had bilaterally enlarged eye muscles, one of which was the patient with positive TSI. The remaining 6 patients had unilateral extraocular muscle enlargement. Thus, 2 of 9 patients had ophthalmopathy without thyroid dysfunction so-called isolated autoimmune ophthalmopathy or Graves' ophthalmopathy. Thyroid function tests seem to be of limited value in the diagnosis between endocrine and non-endocrine eye disease, and we recommend the use of diagnostic imaging (e.g. CT-scan) in patients with unilateral exophthalmus in order to diagnose malignant processes.

The autologous mixed lymphocyte reaction (AMLR), i.e. the ability of T lymphocytes to proliferate when cultured with autologous non-T cell fractions, is an 'in vitro' phenomenon showing immunological memory and specificity, probably related to the cooperation ability of immunocompetent cells. We have evaluated AMLR in 27 patients with Graves' disease of varying clinical status (untreated and treated with antithyroid drugs, surgery or 131I). The results obtained show: Impaired AMLR in untreated patients (as in other autoimmune diseases). Significantly higher AMLR in cured patients, and that AMLR in cured patients varies with the treatment (higher after surgery or radioiodine than after medical treatment). These results are consistent with the hypothesis of a functional defect of T cells in Graves' disease, which improves when clinical remission is achieved.

Fifty-four patients with diffuse non-toxic goitre were observed before and under therapy either with 125 micrograms LT4 (group A) or 75 micrograms LT4 + 15 micrograms LT3 (group B) in a prospective double blind study, using 1-, 3- and 6-months controls. Changes in goitre size have been estimated by ultrasonic scanning. Both treatment forms provided a significant reduction of goitre size, even after 1 month of therapy: a 20%-decrease in group A and 16% in group B. The 6-month reduction was about 30% in group A and 27% in group B. Between the 2 groups there were no differences in the reduction of volume. The suppression of the TSH-response to TRH was identical in both groups, too. In group A there was a predominant increase of the TT4- and FT4-serum levels, both reaching the hyperthyroid range. In group B there was a predominant increase of the TT3- and FT3-serum levels and a slight increase of the FT4-levels. The TT3- and FT3-serum levels also exceeded the upper normal range. As the blood samples were drawn about 2 h after medication, acute hormone resorption influenced these data. In the 3-month controls only there was a significant correlation between the reduction of the thyroid volume and the suppression of TSH-release. In the 6-month controls we found a weak correlation of the reduction of volume and the decrease of the pertechnetate uptake value.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of T3, T4, FT4 and TSH were determined in 9 euthyroid patients during 6 h after intake of morning thyroxine replacement medication. Four hypothyroid patients were studied in the same way after the intake of 50 micrograms thyroxine. In the euthyroid patients the FT4 level increased by 31%, while the increase of T4 was 16% and the increase of T3 11%. In the hypothyroid patients levels of T3, T4 and FT4 did not change after ingestion of 50 micrograms thyroxine, while the TSH level was decreased by 30%. It is concluded that during thyroxine replacement therapy hormone analysis must be interpreted in relation to the time of thyroxine administration.

The seasonal variations of iodothyronines and TSH serum concentrations were evaluated in 24 healthy subjects of both sexes. Using a 12 month cosine function, a significant circannual rhythm was found in T3, T4 and free T4 whose maximal values were found in September for T3, in August for T4 and in October for free T4. No significant seasonal variations in free T3 or TSH were found. Some circannual but not sinusoidal changes were found for reverse T3 and TBG. A positive linear correlation between T4, T3 and reverse T3 changes was observed, indicating that the sinusoidal oscillations of these hormones were in phase with each other. Relative weight was significantly lower in summer than in winter, though spontaneous caloric intake and physical activity did not change. A slight but significant correlation was found between relative weight and T4, free T4 and reverse T3 values measured during the period of study.

A series of 91 patients operated on for non-toxic goitre was followed systematically during 24 months post-operatively with regard to thyroid function. A thyroid remnant of at least 5 to 8 g was left in the majority of cases, and thyroid replacement was not given. Histopathological grading was performed on goitrous specimens with reference to lymphocytic infiltration. Thyroglobulin antibodies and thyroid microsomal antibodies were determined pre-operatively. Goitre resection provoked a high, but transient increase in serum thyroid stimulating hormone (TSH) levels with peak values 3 to 6 months after operation. Twenty-four months after surgery serum TSH values had normalized, but were still slightly elevated in patients with bilateral surgery and high lymphocytic infiltration, 9% of the patients. The concentration of serum free thyroxine index (FT4I) and serum total triiodothyronine (TT3) decreased after operation, but within reference range. Twenty-four months after surgery, serum FT4I was back to baseline values, while serum TT3 was still lowered compared to the pre-operative level. None of the patients developed overt hypothyroidism. Occurrence of circulating thyroid autoantibodies was not related to post-operative changes in thyroid parameters. We conclude that thyroid replacement therapy seems not to be indicated routinely following resection for non-toxic goitre, but precaution should be taken in case of bilateral resection and high lymphocytic infiltration of goitrous specimens.

Earlier studies of the effect of glucocorticoids on thyroid function tests have given different results. This may be due to the fact that varying corticosteroid doses have been used. The present study examined four groups of healthy volunteers, who were given betamethasone in increasing doses (1.5, 3.0, 4.5 and 6.0 mg daily) for 5 days. Definite dose-response relations were found for rT3. The results obtained explain previous variable results. Oral corticosteroids also affected the concentrations of the thyroid hormone-binding proteins but no clear-cut dose-response relation were observed.

Plasma concentrations and anterior pituitary content of growth hormone (rGH), thyroid stimulating hormone (rTSH), and rat prolactin (rPrl) as well as the plasma concentrations of triiodothyronine (T3), thyroxine (T4) and somatomedin A (SM-A) have been determined in intact, castrated or hysterectomized adult rats with and without treatment with steroid-free, crude uterine extracts. Hysterectomy caused a significant increase in the plasma GH but decrease in the plasma TSH concentrations. Injection of crude, steroid-free uterine extracts for 14 days had the following effects: decreased plasma GH concentration of intact rat and anterior pituitary GH content of both intact and castrated animals; increased plasma TSH and T3 concentrations above the ovariectomized control; decreased pituitary content of prolactin in castrated rats. The plasma levels of immunoreactive somatomedins A were negatively correlated to the plasma GH concentrations but positively correlated to the body weight. It was concluded that the uterus is not only a target for different endocrine influences but contains biologically active, non-steroidal substances which have a complex effect on the endocrine system of adult, female rats.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.

The functioning of the hypothalamo-pituitary-target organs axis was assessed in 3 patients with 'fertile eunuch' syndrome (FE) and 6 patients with 'classic' hypogonadotrophic hypogonadism (HH) with or without hyposmia. Both groups of patients did not differ from each other with regard to basal serum prolactin levels, pituitary growth hormone and thyrotrophin reserve and the thyroid or adrenal gland function. Both groups differed, however, with respect to the hypothalamo-pituitary-gonadal function: 1. the pituitary LH response to exogenous LH-RH was (low)-normal in FE and blunted in HH; 2. the basal FSH levels were normal in FE and undetectable in HH; 3. the basal LH levels were normal in FE and 3/6 patients with HH and low in the remaining three; 4. the basal and HCG stimulated plasma testosterone concentrations were significantly higher in FE than HH. The data suggest that FE represents a less severe form of LH-RH deficiency, rather than a distinct disorder.

Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 +/- 2 mW/l erythrocytes which was higher than the post-treatment value of 99 +/- 2 (P less than 0.001) as well as the value for 14 euthyroid subjects, 108 +/- 2 mW/l (P less than 0.001). The NaF inhibitable rate was 73 +/- 2 before and 63 +/- 1 mW/l after therapy (P less than 0.01). These values correspond to 61 +/- 1 and 64 +/- 1% (n.s.) of the total heat production rate, and were similar to that of 61 +/- 2% for the controls. Heat production rates in the presence of NaF were 47 +/- 1 before and 36 +/- 1 mW/l after therapy (P less than 0.001), representing 39 +/- 1 and 36 +/- 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.

The serum concentration of sex-steroid-binding plasma protein (SBP) was measured with radioimmunoassay for 92 patients with Graves' disease, 36 males and 56 females, as well as 92 age- and sex-matched controls. In 24 male patients with hyperthyroidism, the mean SBP concentration was 6.4 +/- 0.2 (mean +/- SD) microgram/ml, whereas it was 2.3 +/- 0.2 micrograms/ml for the controls. The mean SBP concentration in 28 female patients with hyperthyroidism was 7.4 +/- 0.6 micrograms/ml, whereas it was 3.2 +/- 0.6 micrograms/ml for the controls. In Graves patients who were euthyroid following treatment, SBP levels were decreased near normal in both sexes. There was a significant correlation between T4 and SBP concentrations as well as between T3 and SBP concentrations in patients with Graves' disease in both sexes, with a better correlation in females. Increased SBP in untreated Graves' disease initiated to decline within a month following administration of antithyroid drugs, taking over 3 months to decline to the normal range.

Effects of a 72-h prostacyclin (PGI2) infusion (5 ng/kg/min) on hormone levels were studied in 11 patients (5 males, 6 females) suffering from obliterative arterial disease of the lower extremities. ACTH, cortisol, TSH, prolactin (Prl), GH, LH, FSH, T3, T4, calcitonin, parathyroid hormone (PTH), insulin, plasma renin activity (PRA), aldosterone and testosterone levels were measured at -15, 0, 30, 120, 240 min and 24, 48, 72 and 96 h after the infusion. During the first 240 min Prl and GH levels showed an increase that was thought to be either an effect of release of hormones or a consequence of stress. At the same time the thyroid hormones, T3, T4 and calcitonin decreased, presumably owing to an alteration in the blood flow to the thyroid gland. All these hormone levels returned to normal at 24 h in spite of the infusion continuing. PRA increased only during the second half of the infusion. No changes were found in the levels of ACTH, cortisol, TSH, LH, FSH, PTH, insulin, aldosterone and testosterone during the infusion. Five diabetics showed the same hormonal changes as the non-diabetics and their blood sugar levels remained unaffected during and after the procedure.

A 74 year old woman was found to have elevated serum thyroid-stimulating hormone (TSH) levels and elevated serum thyroid hormone levels, with clinical euthyroidism. There was no evidence of a pituitary tumor. TSH levels increased substantially during methimazole therapy. Administration of dexamethasone was followed by a prompt fall in serum TSH levels. Triiodothyronine (T3) was administered over a period of 20 days in doses from 25 micrograms to as much as 100 micrograms daily causing a rise in serum T3 above 700 ng/100 ml, a decline of T4 and a blunting of the response to thyrotrophin-releasing hormone (TRH), with normal metabolic responses (pulse rate, photomotogram, cholesterol). These results suggest that the patient's disorder is due to partial target organ resistance to thyroid hormones.

Serum levels of thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were studied in 80 patients with endogenous depression before and after electroconvulsive treatment (ECT). Compared to the values found after recovery, the patients when depressed had significant increased serum levels of T4, rT3, 3,3'-T2 and 3',5'-T2. Serum concentrations of T3 and 3,5-T2 were not significantly altered. Similarly the free T4 index (FT4I) was increased, while the free T3 index (FT3I) was unaffected. Previous studies have shown a reduced TSH response to TRH in patients with endogenous depression and that the long-term outcome after ECT is strongly related to changes in the TSH response. However, patients with increased TSH response to TRH (n = 23) had a pattern of serum iodothyronine concentrations similar to those (n = 57) with an unchanged TSH response. A similar pattern was also found in 7 patients with nonendogenous psychosis, in whom the TSH response to TRH was unchanged after recovery. It is concluded that the alterations of the TSH response to TRH found in endogenous depression cannot be explained by changes of FT4I or FT3I.

Serum total and free T4 and T3, thyroxine-binding globulin (TBG) and TSH, basal and 20, 30 and 60 min after TRH (200 micrograms, iv), were evaluated in 125 hypothyroid patients (38 with severe, 23 with mild, and 64 with subclinical hypothyroidism), in 35 euthyroid subjects with autoimmune thyroiditis, and in 51 healthy controls. T4/TBG and T3/TBG ratios were also calculated. A significant decrease in all indices of thyroid function except for T3 occurred simultaneously with a significant increase in basal and TRH-stimulated TSH levels from healthy subjects to subclinical hypothyroids, from subclinical to mild and from mild to severe hypothyroids; euthyroid patients with autoimmune thyroiditis did not differ from healthy subjects. All severe hypothyroid patients had low T4 as well as free T4 (FT4), free T3 (FT3), T4/TBG and T3/TBG ratios, but among mild and subclinical hypothyroids direct determination of FT4 and FT3 proved to be a better index of thyroid function than determination of T4 and T3 even after correction for TBG levels. FT4 was the most commonly abnormal index (19 of 23 subjects with mild and 14 of 64 with subclinical disease). Regression analysis showed that FT4, T4/TBG ratio, T4, and FT3 had a significant inverse correlation with TSH in hypothyroid patients. Discriminant analysis showed that among the thyroid parameters, FT4 is the variable which discriminates best between control subjects and the 3 groups of hypothyroid patients. These data extend previous reports and in a large series of patients confirm the biological meaning and the clinical value of direct measurement of serum free thyroid hormones in hypothyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Unlabelled: To obtain more information about a possible role of somatomedins in mediating the effects of thyroid hormones on the development and function of epiphyseal cartilage, somatomedin activity, measured on the basis of 35S incorporation in embryonic chick cartilage, was studied in thyrotoxic patients before and after treatment with carbimazole or surgery and in a group of patients with primary hypothyroidism. In 29 hyperthyroid patients mean values of somatomedin were 1.29 +/- 0.03 SEM an differed significantly (P less than 0.01) from normals (1.04 +/- 0.03). In 15 carbimazole treated patients and in 5 operated patients with thyrotoxicosis somatomedin levels fell from 1.29 +/- 0.04 to 1.03 +/- 0.04 (P less than 0.01) when the patients became euthyroid. Correspondingly, somatomedin levels in 12 untreated hypothyroid patients (0.82 +/- 0.04) were significantly less than in normals (P less than 0.01) an increased from 0.77 +/- 0.09 to 1.14 +/- 0.13 (P less than 0.05) in 4 patients on replacement therapy., In Conclusion: somatomedin levels rise when thyroid hormones are present in excess, and fall when these are deficient. This suggests that thyroid hormones are important regulators of somatomedin levels.

In order to study the hypothalamic-pituitary-thyroid function in children with chronic renal failure (CRF), the serum levels of L-thyroxine (L-T4), L-triiodothyronine (L-T3), reverse T3 (rT3), thyrotrophin (TSH) and prolactin (Prl) were measured by radioimmunoassay (RIA). Values were compared with those of normal subjects. Low levels of L-T4 were present in CRF patients as compared to controls. L-T3 was also found to be low but less than L-T4, and rT3 was lower in patients with long evolution. No alterations were observed in TSH basal levels, whereas Prl values in patients were high. After thyrotrophin-releasing hormone (TRH) administration, TSH and Prl rose to similar levels in both groups, but high values were maintained throughout (120 min) in CRF. A significant negative correlation was found between the peak rise of the TSH response and the CRF evolution time. The L-T3 response to TRH administration (120 min) was similar in both CRF and controls. The rate of in vivo and in vitro exogenous TRH degradation was decreased in patients with CRF or by their sera, respectively. Our data seem to confirm that the hypothyroid syndrome described in CRF patients is of hypothalamic origin, and the low in vivo and in vitro TRH degradation rates are a consequence of this state.