摘要:

SUMMARYThe thyroid glands of two hypothyroid goitrous siblings aged 13 and 14 and of a 21‐year‐old hypothyroid goitrous female were examined. In all three patients a very high thyroid uptake of iodide was observed in the presence of a negative perchlorate discharge test. An abnormally high serum protein bound iodine (12·9–20·0 μg/dl) and low serum T4 concentration suggested the presence of increased serum levels of iodoalbumin. Surprisingly, serum T3 levels were normal or low normal (80–220 ng/dl) in several determinations. Basal serum TSH was elevated and an exaggerated TSH response was observed after TRH. Serum thyroglobulin was undetectable in one patient, low normal in another and in the normal range for the third one. Except for the patient with undetectable Tg the two other subjects slightly increased the serum Tg levels after a bovine TSH injection. Plasma chromatography after a tracer dose of125I disclosed only minute amounts of T3+T4 and MIT+DIT. Studies performed in the homogenized thyroid tissues indicated that these goitrous glands had pronounced decrease of immunoreactive thyroglobulin. The total amount of Tg‐like proteins (RIA) in the thyroid soluble protein extract was only 16–122 μg/g (normal: 50–70 mg/g of tissue). Ultracentrifugal studies were unable to demonstrate the presence of mature (18–20S) thyroglobulin. Only one peak (3·6–4·1S) was obtained in the pooled soluble proteins supernatants. Hydrolysis of the homogenates indicated, by subsequent column chromatography, very low relative concentrations of iodotyrosines and iodothyronines and that a relatively large amount of iodide remained associated with subcellular proteins and undigested. The predominant histological pattern was of the intermediary differentiated adenoma type, microfollicular or fetal, with several atypical features and capsular invasion which may suggest malignant change. We conclude that a defective Tg export from the cell to the lumen or an anomaly in the structural gene leading to inadequate translation of Tg mRNA finally results in deficient storage of normal, mature Tg in the colloid with subsequent

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00113.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYThe inhibitory role of the dopaminergic and opioidergic mechanisms in the control of LH secretion in patients with polycystic ovary syndrome (PCO) was evaluated. The administration of an opiate receptor antagonist, naloxone, of a dopamine receptor antagonist, metoclopramide, or of human synthetic βh‐endorphin, were unable to alter LH secretory activity in patients with PCO. Since identical doses of these antagonists and the opiate agonist have elicited respectively a rise and fall of LH levels in normal cycling women, these findings suggest that an underlying hypothalamic component of defect in endogenous dopamine and opioid control may be responsible for the inappropriate gonadotrophin secretion in this syndro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00114.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYEight adult male patients suffering from hydrocephalus of differing aetiologies were investigated in order to detect the existence of diurnal variations of prolactin (PRL) concentration in human cerebrospinal fluid (CSF). Blood and ventricular CSF samples were taken every 2 h during the day (0800–2200 h) and every hour during the night (2300–0700 h). CSF mean PRL levels showed significant nyctohemeral variations with low levels (2·1 ± 0·3 ng/ml) during day‐time and higher levels at night (3·3 ± 0·1 ng/ml), similar to that observed in serum (PRL values: 16·4 ± 5·2 and 24·8 ± 4·3 ng/ml during day and night periods respectively). The presence of a 24 h CSF PRL secretory profile similar to that in serum was shown in six patients with normal 24 h mean PRL values and normal diurnal changes in serum. In two patients with an altered serum 24 h secretory pattern no significant nyctohemeral variations in CSF PRL levels were found. Present data show the existence in man of nyctohemeral variations in CSF PRL content related to the 24 h changes of PR

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00115.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYThyroid function has been investigated in 24 young military cadets participating in a 5 d ranger training course with heavy physical excercise, calorie deficiency and deprivation of sleep. The cadets were divided into three groups, each differing in the amount of sleep and food consumption. The serum levels of thyroid hormones (T4, FT4, T3, rT3) and TBG showed a biphasic pattern during the course. Initially there was an increased secretion concomitant with an increased deiodination of T4 to T3 and rT3 mainly due to physical exercise. When the activities lasted for several days without sufficient food supply the thyroid secretion decreased simultaneously with an alteration of the peripheral conversion of T4 to rT3 instead of T3. A significant correlation was found between the changes in total and free thyroxine (r= 0·9) and between the increase in rT3 and decrease in T3 (r= 0·6). TSH decreased during the first day of activities and remained low throughout the course. The TSH response to TRH stimulation was greatly reduced during the course due to physical exercise and calorie deficiency. The present investigation demonstrates that the thyroid function is strongly affected by prolonged physical exercise and a negative energy balance, whereas sleep deprivation does not have any significant influence. The results indicate that the alteration observed is not regulated just by the hypothalamo‐pituarity‐thyroid‐axi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00116.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYDecreased insulin binding to receptors is associated with the insulin resistance of obese and non‐obese non‐insulin‐dependent diabetics. ‘Down Regulation’ by elevated insulin levels has been suggested as the cause, but factors influencing receptor affinity have not been examined. To investigate the control of receptors in diabetes, 10 non‐insulin‐dependent diabetics and 10 normal subjects were studied after 6 d on low and 6 d on high calorie diets of fixed composition (700 and 2800 Kcal/70 kg of ideal body weight). The binding of insulin by erythrocytes of non‐diabetics, as predicted, increased on the low and decreased on the high calorie diets, due to altered affinity. In contrast, the binding in the diabetics did not change significantly, and the responses to the low and high calorie diets were less than in the normal subjects (P<0·05 andP<0·001 respectively). Indeed, the insulin binding in all 5 non‐obese diabetics changed in the opposite direction (P<0·01) to the non‐diabetics, whereas the obese diabetics showed a mixed response. The changes in receptor binding in the diabetics was completely unrelated to the diurnal plasma insulin levels during 24 h studies. We conclude that the dietary regulation of erythrocyte insulin receptor affinity in non‐insulin‐dependent diabetes is abnormal, and insulin receptor affinity is regulated by factors other than insulin. The relation of this abnormality to the insulin resistance n

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00117.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYImmunoregulatory defects have been suggested in autoimmune disorders including GRAVES' disease. The finding that Concanavalin A‐induced suppressor T cell function was sub‐optimal in GRAVES' disease has been disputed; a restricted defect in TSH‐receptor antigen‐specific suppressor cells has instead been proposed by Okitaet al.(1980). To explore this further, we studied both specific and non‐specific suppressor cell function in a pair of HLA identical twins, one of whom had GRAVES' disease. By contrast to the euthyroid healthy twin and 10 healthy controls (612 cpm/106cells) the patient's mononuclear cells (MNCs) incorporated more {3H}‐thymidine (7365 cpm/106cells) in response to thyroid membrane antigen (TMA). Removal of glass‐adherent cells before addition of antigen increased {3H}‐uptake by cells from the healthy twin to 1808 cpm but reduced those from the GRAVES' twin to 3411 cpm. The influence of MNCs cultured with Con A or TMA for 24 h upon {3H}‐thymidine uptake by 2 × 106indicator cells triggered by Con A for 72 h or TMA for 96 h was taken as a measure of non‐specific and specific suppressor cell function respectively. Both Con A and TMA induced suppressor cells were reduced, the latter to a more marked degree, in the patient compared to the healthy twin; mixing of MNCs from patient and healthy twin in a 1:1 ratio improved the patient suppressor cell function. When the patient's MNCs triggered for 24 h with Con A were mixed in a 1:1 ratio with her fresh MNCs and TMA, less blast transformation was found compared to an equal number of fresh cells (3H‐thymidine uptake 3250 vs 7365 cpm/106). Similarly, preincubated cells from the healthy twin had greater suppressive effect (1820 cpm/106cells). We conclude that (I) the HLA identical healthy twin has TMA autoreactive lymphocytes regulated by adherent regulatory cells; (2) the increased ratio of helper/suppressor cells in the adherent cell population in the patient leads to a decrease of {3H}incorporation upon their removal; (3) in the patient, the specific suppressor cell defect is more severe than the non‐specific defect; (4) lack of specific TMA induced triggering may be the critical immunoregulatory d

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00118.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYSix hundred and forty‐three neonates from mothers with GRAVES' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6·0% (three of 50), 0·3% (one of 350), 1·7% (two of 117) and 0·0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P<0·01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect,

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00119.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYHigh plasma noradrenaline (PNA) levels have been reported in hypothyroid patients and hypothyroidism has been associated with hypertension. To explore the relationship between PNA and blood pressure (BP) in hypothyroid patients, and the effects of gradual thyroxine replacement, a prospective study was performed comparing BP, heart rate (HR) and PNA in a normotensive and a hypertensive group of hypothyroid patients before and during gradual thyroxine substitution. Thyroxine treatment reduced the BP; the reduction in supine BP was greater in the hypertensive than in the normotensive group. HR increased similarly in both groups during treatment. PNA was elevated in the normotensive group before treatment and decreased gradually during thyroxine treatment. The hypertensive group had normal PNA levels. The present study indicates that normotensive, in contrast to hypertensive, hypothyroid patients have increased sympathetic nervous activity. Although the mechanism is unclear, thyroid replacement therapy can reverse hypertension in hypothyroid patients.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00120.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYTotal plasma cortisol measurements may be misleading when there are variations in the plasma cortisol‐binding protein capacity resulting from drugs, pregnancy or congenital alterations in cortisol‐binding globulin (CBG). Salivary cortisol levels, which represent the free component of plasma cortisol, are less affected by alterations in protein binding and have been used in the investigation of hypothalamic‐pituitary‐adrenal disorders. This study compares these two indices of adrenal function in conditions of true hypercortisolism and spurious hypercortisolism (resulting from oral contraceptive medication or pregnancy). The circadian variation of cortisol in plasma and saliva was studied in six patients with unequivocal hypercortisolism and compared with normal volunteers. In the normal group, plasma and salivary cortisol levels taken at 0900 h were significantly higher than those taken at 2400 h. Patients with Cushing's syndrome failed to show a significant difference between plasma and salivary cortisol levels collected at 0900 and 2400 h. Five patients with pituitary‐dependent Cushing's disease, one patient with an adrenal carcinoma causing Cushing's syndrome and seven normal subjects each received a dexamethasone suppression test using a continuous infusion of dexamethasone sodium phosphate at a rate of 1 mg/h. There was no significant difference in the half‐life disappearance rate of endogenous cortisol in either plasma or saliva comparing grouped data from patients with pituitary‐dependent Cushing's disease with that of normal subjects. Failure of suppression of both plasma and salivary cortisol levels was observed in the one patient with adrenal carcinoma during dexamethasone infusion. The correlation between plasma and salivary cortisol measurements during the dexamethasone infusion was r=0·989 (P<0·001) for normals andr= 0·982 (P<0·001) for Cushing's patients. Measurements of plasma and salivary cortisol were compared in pregnancy and during low dose oestrogen therapy; both these conditions are known to be associated with elevated cortisol binding globulin concentrations. A significant difference was demonstrated between the 0900 h plasma cortisol levels of normal subjects and those both in the third trimester of pregnancy of the oestrogen containing contraceptive pill. No difference was observed in the 0900 h salivary cortisol between control and pregnant or oestrog

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00121.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY

摘要:

SUMMARYSerum concentrations of testosterone and dehydroepiandrosterone sulphate (DHAS) have been measured in 10 stable insulin‐dependent diabetic (IDD) males (chronological age (CA) range 13·0‐17·5 years). Their results have been compared with those of a control population of 69 non‐diabetic males who presented with mild constitutional growth delay and whose skeletal maturity and pubertal development were similar to the diabetic subjects. Within bone ages (BA) 11·0–14·5 years no significant difference was observed between the serum testosterone concentrations of the diabetic patients and controls: diabetic males, 8·2 (0·3–25) nmol/1 (median and range); controls, 7·0 (<0·3–23) nmol/1. In contrast, within BA 11·0–14·5 years, the diabetic males had significantly lower serum DHAS concentrations: diabetic males, 1·1 (0·7–4·2) μmol/1; controls, 3·7 (0·7–5·6) μmol/1 (P<0·001). The serum DHAS concentrations of the diabetic males were also significantly lower than the controls when matched separately for pubic hair and genital development, testicular volume and serum testosterone, (in each comparisonP<0·02). Serum DHAS concentrations of the diabetic males did not correlate significantly with CA, BA, BA delay (CA‐BA), age of onset of diabetes, duration of diabetes, or glycosylated haemoglobin (GHb), but significant correlation was observed between BA delay and duration of diabetes,r= 0·65,P<0·05. We conclude that gonadarche appears to proceed despite delayed adrenarche in IDD males. This study presents further evidence in favour of adrenarche and gonadarche being independent physiological events. The causes and clinical significance of low serum DHAS concentrations in adolescen

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1984.tb00122.x

出版商:Blackwell Publishing Ltd    

年代:1984

数据来源: WILEY