Hypothalamic-pituitary-thyroidal dysfunctions in anorexia nervosa

There are clinical similarities between anorexia nervosa and hypothyroidism. Circulating levels of T4 and particularly T3 have been reported to be low in this eating disorder. Previous reports have, however, shown normal basal levels of serum TSH with normal or delayed responses to TRH. To assess thyroid function and the hypothalamic-pituitary axis in 21 women with anorexia nervosa, serum levels of free and total thyroid hormones, binding proteins, and TSH employing an extremely sensitive assay (detection limit = 0.02 microU/ml) were measured. Serum T4, free T4, T3, free T3, TSH, TBG and TBPA concentrations were significantly lower and rT3 levels were significantly higher in anorexia nervosa patients than in normal controls. A delayed TSH response to TRH was noted in 66% of patients, hyporesponsiveness was seen in another 24%, and a normal response in only 10%. In 10 anorexia nervosa patients studied after weight gain, T4, T3, free T3, TSH, TBG and TBPA were significantly increased, and rT3 was significantly decreased. No change in mean free T4 levels with weight gain was noted. Other parameters of hypothalamic dysfunction in anorexia nervosa have been reported and the present data suggest that apparent hypothalamic hypothyroidism occurs perhaps as an adaptation to prolonged starvation.     

羊水中甲状腺激素检测及其临床应用

采用体外放射分析方法对２２例正常和３０例正在治疗的患甲状腺疾病的孕妇羊水Ｔ３、Ｔ４、ＴＳＨ、ｒＴ３及ＦＴ３、ＦＴ４进行了测定。并监测孕妇妊娠期甲状腺功能和进行了新生儿甲低筛查。结果表明羊水中甲状腺激素水平的测定,对了解母体服药对胎儿的影响及有无胎儿甲低是有价值的。羊水中ｒＴ３水平的测定可作为观察及筛选胎儿甲低的方法之一。     

Increased Expression of CD25 and HLA-DR on Lymphocytes Recruited into the Peritoneal Cavity in Non-Infected CAPD Patients

The impact of uremia per se, peritoneal dialysis (PD) and hemodialysis (HD) treatment was evaluated on characteristics of lymphocytes. CD4, CD8, CD25 and HLA-DR were analyzed, with flow cytometry, in lymphocytes prepared from peripheral blood of uremic (n = 10) and hemodialysis patients (n = 10). Peritoneal dialysate was also obtained from patients on CAPD (n = 12). A decreased relative and absolute lymphocyte count was observed in peripheral blood from uremic, HD and CAPD patients compared to healthy controls (p < 0.03, p < 0.03 and p < 0.02, respectively). On the other hand, the relative distribution of lymphocytes was significantly higher in peritoneal dialysate compared to peripheral blood of CAPD patients (p < 0.02). Likewise, the absolute CD4 positive lymphocyte count was lower in the peripheral blood from uremic, HD and CAPD patients as compared to healthy controls (p < 0.001, respectively). In CAPD patients the relative distribution of CD4 positive cells (p < 0.001) was lower, while quantitative CD25 level (p < 0.01) and the relative count of HLA-DR (p < 0.0001) was increased in the peritoneal dialysate compared to blood. Taken together a selective activation of lymphocytes in peritoneal dialysate as compared to peripheral blood from uremic, HD and CAPD patients was observed. The altered biological function of the inflammatory cells may therefore explain the increased susceptibility to infectious diseases.     

Thyroid antoantibodies and the response to thyrotropin releasing hormone in patients with subclinical hypothyroidism.

AIM--To evaluate the clinical usefulness of the thyrotropin releasing hormone (TRH) test and estimation of thyroid autoantibody concentrations in patients with borderline raised thyroid stimulating hormone (TSH). METHODS--The records of 34 consecutive patients with persistent borderline increased TSH (4.4-9.9 mU/l) referred to the Medical Investigation Unit were reviewed. The response of patients with thyroid autoantibodies to the TRH test was compared with that of patients with a negative antibody screen. RESULTS--Eleven (44%) of 25 patients with positive anti-thyroid microsomal and/or thyroglobulin antibody tests and three (33%) of nine patients with a negative antibody screen had hypothyroid responses to TRH. Neither age nor sex affected the response to TRH. Basal TSH alone was poorly correlated with these indices. Twelve (35%) patients who had elevated basal TSH had a normal response to the TRH test. CONCLUSION--Patients with positive or negative thyroid autoantibodies and an exaggerated response to the TRH test should be regarded as hypothyroid and treated with thyroxine. Patients with positive thyroid autoantibodies and normal TSH response may subsequently develop hypothyroidism and should be given long term follow up.     

Effects of growth hormone treatment on thyroid function in pediatric patients with Prader–Willi syndrome

It is unclear whether hypothyroidism is present in patients with Prader–Willi syndrome (PWS). This study aimed to clarify the state of the hypothalamic–pituitary–thyroid axis and the effects of growth hormone (GH) treatment on thyroid function in pediatric patients with PWS. We retrospectively evaluated thyroid function in 51 patients with PWS before GH treatment using a thyroid‐releasing hormone (TRH) stimulation test (29 males and 22 females; median age, 22 months). We also evaluated the effect of GH therapy on thyroid function by comparing serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels at baseline, 1 year, and 2 years after GH therapy. TSH, fT4, and fT3 levels were 2.28 μU/ml (interquartile range [IQR]; 1.19–3.61), 1.18 ng/dl (IQR; 1.02–1.24), and 4.02 pg/dl (IQR; 3.54–4.40) at baseline, respectively. In 49 of 51 patients, the TSH response to TRH administration showed a physiologically normal pattern; in two patients (4.0%), the pattern suggested hypothalamic hypothyroidism (delayed and prolonged TSH peak after TRH administration). TSH, fT4, and fT3 levels did not change significantly during 1 or 2 years after GH treatment. The TSH response to TRH showed a normal pattern in most patients, and thyroid function did not change significantly during the 2 years after initiating GH treatment.     

Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation.

To determine the implication of decreased T3 production during fasting, seven normal men were fasted for 80 hours on two occasions; they received 5 microgram of T3 every three hours durnig the second fast. The mean serum T3 concentration declined during the control fast from 120 to 73 ng per deciliter (P less than 0.01), but remained slightly above base-line values during the T3 fast. Mean serum T4 concentrations did not change, and mean serum rT3 concentrations increased, during both fasts. The peak serum TSH increment after TRH was 11.1 micromicron per milliliter before fasting, 8.9 (not significant) after the control fast and 2.2 (P less than 0.01) after the T3 fast. Urea excretion was 9.1 per cent higher during the T3 fast; there were no differences in the changes in blood glucose, plasma fatty acids or other substrates during the two fasts. Pretreatment with potassium iodide lowered serum T4 concentrations and increased the serum TSH response to TRH after fasting. We conclude that the decrease in serum T3 concentrations during fasting spares muscle protein. Fasting is accompanied by a lower set point of TSH secretion, which remains sensitive to changes in serum thyroid hormone concentrations.     

Anorexia nervosa with elevated serum TSH

Low or normal serum TSH concentration is common during fasting and in patients with anorexia nervosa. We report here four patients with anorexia nervosa who had elevated serum TSH, low T3 and low free T4 levels when the initial diagnosis was made. Also, an appearance of TSH peak in response to TRH was delayed, but T3 responsiveness to TRH was normal. All patients were clinically euthyroid with negative serum thyroid autoantibodies and without goiter. Following weight gain, basal levels of serum T3, free T4, and TSH, as well as TSH responsiveness to TRH, returned almost to normal. The data indicated that these patients with anorexia nervosa before refeeding had either a latent transient primary hypothyroidism or the low T3 syndrome associated with an inappropriately high secretion of TSH, probably a new condition that is related to their pretreatment nutritional state.     

老年慢性肺心病的甲状腺功能变化

本文用放免法测定了34例老年慢性肺心病患者的甲状腺激素水平,以探讨老年慢性肺心病人的甲状腺功能状态。结果发现,老年慢性肺心病组血清的TT_3、TT_4均值明显低于健康对照组(p<0.01),而TSH均值二者比较无明显差异。急性发作期组TT_3、TT_4明显下降,尤以TT_3明显,分别为1.04±0.37(nmol/L)和95.83±36.58(nmol/L),缓解期组T_3、T4_均有回升,分别为1.58±0.61(nmol/L)和105±26.66(nmol/L),说明肺心病T_3、T_4下降与肺心病的严重程度有关。急性发作期组TSH与缓解期组及健康人组比较则无明显差异,说明老年肺心病患者的甲状腺功能有一定程度减退。而TSH测定正常,能排除原发性甲状腺功能减退所致的T_3、T_4改变,符合低T_3综合征,提示下丘脑的保护性适应。动态观察血清T_3、T_4的变化,对于判断治疗和预后有一定的价值。     

Changes in erythrocyte calcium and potassium in patients during HD and CAPD

The purpose of this study was to determine the changes in calcium and potassium content in the red blood cells (RBC) of uremic patients during a hemodialysis (HD) session and a 6/hrs CAPD exchange. RBC calcium and potassium were determined in 20 patients on HD in three blood samples collected at 0'-HD (pre-HD), 45'-HD and 240'-HD (end-HD), in 20 patients on CAPD, in two blood samples, collected at 0' time (pre-inflow) and 120', (solution in peritoneal cavity) during a 6/hrs exchange (4 exchanges / 24 h) and in 20 normal subjects. The mean value (+/-SD) of RBC calcium in controls was 15.6+/-3.75 micromol/L, in hemodialysed patients at 0'-HD, 45'-HD and 240'-HD 51.5+/-8.5, 70.4+/-12.5 and 51.1+/-10 micromol/L respectively and CAPD patients at time 0' and 120 of an exchange 53.6+/-23.4 and 70.6+/-9.2 respectively. These values show that RBC calcium in hemodialysed patients is generally significantly higher (p < 0.0001) than in controls. The value at 45'-HD is also significantly higher (p < 0.0001) than at 0' or 240'-HD. In CAPD patients, at 0' and 120' of a 6/hrs exchange, it is significantly higher (p < 0.0001) than in controls, as is the value at 120' (p < 0.001) in comparison to 0'. The mean value (+/-SD) of RBC potassium at the aforementioned time measurements were 95.9+/-3.34, 92.5+/-4.32 and 93.85+/-3.89 mmol/L respectively for patients on HD, 95+/-3.3 and 94.6+/-5.28 mmol/L respectively for patients on CAPD and 99.1+/-3.70 mmol/L in controls. These values show that RBC potassium of hemodialysed patients is significantly lower in comparison to that of controls (0'-HD: p < 0.01, 45'-HD and 240'-HD: p < 0.001); also the value at 45'-HD and 240'-HD is significantly lower (p < 0.001, p < 0.01 respectively) when compared to that at 0'-HD. In patients on CAPD, at 0' time and 120' during 6/hrs exchange, potassium is significant lower (p < 0.001) in comparison to that of controls. In conclusion, uremic patients present high erythrocyte calcium and low potassium with fluctuation during HD-sessions and CAPD 6/hrs exchange.     

Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome.

A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 microU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies. Thyroid ultrasonography and scintigraphy showed hemiagenesis of the left lobe and no evidence of ectopic tissue. TSH response to thyrotropin-releasing hormone (TRH) injection (200 microg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6-2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism. Thyroid function is not a recognized manifestation of WS and is not routinely investigated. However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. Genes mapping at 7q11.23, contiguous to the chromosomal region deleted in most WS patients, may be involved in the development of the thyroid gland, contributing to the complex phenotype of WS.     

血清TSH和Hcy测定在甲状腺功能减退诊断中的价值

目的 分析血清甲状腺激素（TH）和同型半胱氨酸（Hcy）水平测定在甲状腺功能减退诊断中的价值。方法 选取2018年2月~2019年2月在我院诊治的50例甲状腺功能减退患者设为观察组A,40例亚临床甲状腺功能减退患者设为观察组B,另选同期体检正常者40例设为对照组。分别检测三组TH[三碘甲状腺原氨酸（T3）、甲状腺素（T4）、促甲状腺素（TSH）]、Hcy水平并进行比较。结果 观察组B血清FT3、FT4水平与对照组比较,差异无统计学意义（P＞0.05）,血清TSH、Hcy水平高于对照组（P＜0.05）;观察组A血清FT3、FT4水平低于对照组,血清TSH、Hcy水平高于对照组（P＜0.05）;观察组A血清FT3、FT4水平低于观察组B,血清TSH、Hcy水平高于观察组B（P＜0.05）;血清TSH、Hcy变化与临床甲状腺功能减退呈正相关（P＜0.05）;血清TSH、Hcy诊断甲状腺功能减退敏感度和特异度均高于FT3、FT4诊断（P＜0.05）。结论 动态监测血清TSH、Hcy 水平,对亚临床甲状腺功能减退向临床甲状腺功能减退转化具有一定的诊断价值。     

Effect of interleukin-2 and methylprednisolone on in vitro transformation of uremic lymphocytes

The functional relationship in vitro between mitogen-induced lymphocyte transformation, lymphocyte response to interleukin-2 (IL-2) and steroid, and production of IL-2 was examined in patients with chronic renal failure on hemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). The lymphocyte responses to optimal stimulation with phytohemagglutinin, concanavalin A, and pokeweed mitogen were depressed in lymphocyte cultures from HD patients, while CAPD lymphocyte cultures responded normally. However, at suboptimal phytohemagglutinin stimulation both CAPD lymphocyte and HD lymphocyte responses were subnormal. Uremic lymphocyte cultures were more sensitive to the immunosuppressive effect of methylprednisolone. Addition of IL-2 normalized the phytohemagglutinin responses of suboptimally stimulated CAPD lymphocyte cultures and clearly improved the mitogen responses of the HD lymphocyte cultures. Furthermore, the increased uremic lymphocyte sensitivity to methylprednisolone was normalized by addition of IL-2 to the cultures. The measured IL-2 production had clearly decreased in the HD cultures after 48 h as compared to that of the control cultures. A similar but not significant trend was also seen in the CAPD cultures. Thus, it is suggested that a deficient production of IL-2 may partly explain the reduced lymphocyte response of uremic lymphocytes in vitro.     

Endocrine and cytokine changes during elective surgery.

Elective surgery was used as a model of severe non-thyroidal illness (SNTI) to study the inter-relation between changes in serum thyroid hormones, thyroid stimulating hormone (TSH), cortisol, and interleukin 6 concentrations. The study was designed to determine whether the expected interleukin 6 increases after surgery are the cause of decreased serum tri-iodothyronine (T3) concentration normally observed following severe trauma. Blood was sampled for 24 hours before, during, and for 48 hours after abdominal surgery under general anaesthesia in 11 patients. Total T3 decreased 30 minutes after induction and continued to decrease at 24 hours. After a transient increase at 30 minutes, free T3 also decreased, and free thyroxine (T4) concentrations, other than a similar transient increase, did not change. TSH concentrations were increased at four hours and the nocturnal surge was suppressed. The increase in the serum interleukin 6 concentration was not observed until four hours. Cortisol concentrations were increased at 30 minutes and peaked at four hours. Therefore, the early changes in thyroid hormones and TSH accompanying surgery do not seem to be caused by changes in interleukin 6 concentrations.     

甲状腺功能减退症替代治疗的研究现状

长期以来国内外学者对于甲状腺功能减退症的替代治疗是采用标准化的左旋甲状腺素(L evothyroxine,L- T4 )替代治疗方案。然而最近的临床研究表明标准化的L- T4替代治疗不能完全缓解患者的症状,而应用L- T4 /T3的方案替代治疗才能完全缓解患者的症状。进一步的动物实验研究也证实单纯的L- T4治疗不能使甲状腺切除鼠血清中以及大多数组织中T4、T3的含量达到正常,要使机体组织中的T4、T3水平达到正常水平则需要增加L- T4的用量,那样又会导致促甲状腺激素(Thyroid stim ulating hormone,TSH)受抑制,引起亚临床甲亢的相关组织学表现,而使用L- T4 /T3联合治疗的方案能够使血清和大多数组织中的T4、T3水平达到正常。如果人体也相似的话,那么联合L- T4 /T3替代治疗可能是更符合生理需要的治疗方案。为此我们综述了这方面的动物实验研究和临床调查研究的进展状况。     

Thyroid hemiagenesis and elevated thyrotropin levels in a child with Williams syndrome

A girl with Williams syndrome (WS) presented with elevated thyrotropin (TSH) levels (7.0 μU/ml), normal free thyroid hormone concentrations, and absent antithyroid autoantibodies. Thyroid ultrasonography and scintigraphy showed hemiagenesis of the left lobe and no evidence of ectopic tissue. TSH response to thyrotropin-releasing hormone (TRH) injection (200 μg/mq, i.v.) was exaggerated and prolonged, suggesting subclinical hypothyroidism. The biological activity of circulating TSH was slightly below the normal range [TSH bioactivity (B) to immunoreactivity (I) ratio (TSH B/I) = 0.4, normal: 0.6–2.2]. These abnormalities are similar to those seen in patients with hypothalamic hypothyroidism. Thyroid function is not a recognized manifestation of WS and is not routinely investigated. However, abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis and thyroid dysgenesis have been found in other WS cases. Genes mapping at 7q11.23, contiguous to the chromosomal region deleted in most WS patients, may be involved in the development of the thyroid gland, contributing to the complex phenotype of WS. Am. J. Med. Genet. 85:491–494, 1999. © 1999 Wiley-Liss, Inc.     

Thyroid hormones and thyroxine-binding globulin in relation to liver function and serum testosterone in men with alcoholic cirrhosis

In 73 euthyroid male patients with histologically verified alcoholic cirrhosis, thyroid hormones, thyroxine-binding globulin (TBG) and testosterone concentrations (total, non-protein- and non-SHBG-bound) were studied in relation to each other and to the degree of liver dysfunction. Serum concentrations of triiodothyronine (T3) decreased significantly (p less than 0.05) and thyroid-stimulating hormone (TSH) increased with progressing liver dysfunction. Serum concentrations of tetraiodothyronine (T4), TBG and T4/TBG ratio did not correlate significantly with liver function. Serum T3 concentrations correlated significantly (Kendall Tau-beta = -0.33, p = 0.001) with total serum testosterone concentrations, while there was a negative correlation (Kendall Tau-beta = -0.20, p = 0.025) between testosterone and TSH values. No correlation was found between testosterone concentrations and serum levels of TBG. It is proposed that the association between T3 and TSH on one hand and testosterone concentrations on the other reflects a covariation of these variables with liver function. The TBG level was normal in most patients and was not correlated to testosterone concentrations.     

Bromine and thyroid hormone activity.

AIMS--To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS--Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS--The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION--An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity.     

Thyroid function tests

About 80% of thyroid disease consists of thyroid-specific autoimmune diseases, Hashimoto's disease and Grave's disease. To diagnose thyroid diseases, testings for (1) thyroid function and (2) pathogenetic autoantibodies are indispensable. To assess thyroid function, serum hormone concentrations, such as TSH, FT4 and FT3 are measured. Among these hormones, serum TSH concentrations are the most reliable and informative regarding thyroid function, correcting indicating a hyperthyroid, euthyroid or hypothyroid state. Therefore, TSH measurement appears to be the first choice in selecting the hormone determination. Reference intervals for normal healthy subjects of TSH are around 0.4-5.0 microU/ml. The second choice for thyroid function assessment are FT4 which supersedes total T4(TT4). TT4 is affected by changes in serum thyroid hormone binding proteins(TBG, TTR, Albumin). For example, euthyroid pregnant women whose serum TBG are physiologically higher than those of non-pregnant women show augmentation of TT4. However, FT4 depicts within reference intervals, although measurement of FT4 alone is unable to detect any abnormality of thyroid hormone binding proteins. According to its plasma concentration and binding affinity, FT3 measurement deserves no more significance than T3. Another important test for thyroid diseases is to detect serum autoantibodies against thyroid tissues, such as TgAb, TPOAb. Much more important is TSH receptor antibody which differentiates Graves' disease from Hashimoto's thyroiditis. In patients who show hyperthyroidism and some very uncommon hypothyroidism, TSH receptor antibodies should be measured. Three indicators are available as routine tests; TRAb measured by radioreceptor assay; TSAb determined by bioassay using cultured porcine thyroid cells. Usually, TRAb activity clinically correlates well with TSAb. TSBAb was initially discovered in patients with severe hypothyroidism with atrophic thyroid gland. TSBAb blocks thyroid stimulating activity of TSH and consequently causes severe hypothyroidism. TRAb and TSAb are very useful to diagnose and follow patients with Grave's disease.     

北京地区5万例新生儿“甲低”足跟血促甲状腺素筛查结果分析

采用干血滴纸片法测新生儿出血后７２小时足跟血的促甲状腺素作为筛选指标。共筛选新生儿５１５８２名，超出筛查均值的异常者随访昨查血清三碘甲状腺原氨酸，甲状腺素及ＴＳＨ含量，查出先天性甲低患儿１０名，提示检测足跟血中的ＴＳＨ含量作为筛查指标是可靠的。     

Muscle water and electrolytes in patients undergoing continuous ambulatory peritoneal dialysis

Muscle water and electrolytes were determined in percutaneous muscle biopsy material from m. quadriceps femoris in 33 uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 1-38 months, and in 34 normal subjects. The patients showed increased muscle contents of water, sodium, and chloride relative to fat-free solids (FFS); both intra- and extracellular water contents were increased. The total water content was inversely correlated with the duration of CAPD. The muscle potassium content was increased, both relative to FFS and to magnesium, whereas the intracellular potassium concentration was normal. Despite hypermagnesemia, the muscle content of magnesium was normal and the intracellular concentration was even slightly decreased due to the increase in intracellular water. We conclude that muscle water and electrolyte status is abnormal in CAPD patients, but the alterations appear to be less marked than in uremic patients undergoing other forms of therapy.