Levels of testosterone, allopregnanolone and homocysteine in severe hypothyroidism.

Hypothyroidism is very often associated with cardiovascular diseases and neurological complications. Recently, homocysteine has been studied as an independent risk factor for atherosclerosis which negatively affects vascular endothelial cells. Because homocysteine metabolism is related to thyroid and steroid hormones, we studied these relationships in severe hypothyroidism and in euthyroid state. Homocysteine, testosterone and allopregnanolone concentrations were measured in the fasting plasma from 16 women who underwent total thyroidectomy, and who were either hypothyroid or euthyroid. Although all women used oral contraceptives, they were not protected against hyperhomocysteinemia during hypothyroid state. With the normalization of thyroid hormone concentrations homocysteine levels decreased to normal levels. There was a positive correlation between testosterone and homocysteine in the euthyroid state which suggests that not only estrogens but also androgen state should be considered in future studies on homocysteine.     

TSH may not be a good marker for adequate thyroid hormone replacement therapy

The objective of this study was to evaluate parameters of thyroid function and indices of peripheral thyroid hormone action (such as SHBG) in patients whose hypothyroidism was considered well controlled under current criteria. Eighty-five patients with T4-treated hypothyroidism, 28 of whom had athyria, were compared with 114 normal individuals with the same TSH levels. T3 levels were significantly lower in hypothyroidism although mean T4 and fT4 levels were significantly higher. Furthermore, mean SHBG levels were significantly lower in hypothyroidism independently of age. The difference remained when stricter criteria for adequate treatment were applied (TSH < 2.5 microgU/ml). Significant negative correlations were found between logTSH and T3. The slopes of the regression lines of T3 to TSH were significantly different in the control group and the hypothyroid group: thus, for the same TSH levels, T3 levels were lower in the hypothyroid group. We conclude that patients with T4-treated hypothyroidism have lower T3 levels, lower T3/T4 ratio and lower SHBG than normal individuals with the same TSH, perhaps indicating relative tissue hypothyroidism in the liver. TSH levels used to monitor substitution, mostly regulated by intracellular T3 in the pituitary, may not be such a good indicator of adequate thyroid hormone action in all tissues. The co-administration of T3 may prove more effective in this respect, provided novel suitable preparations are developed. Until this is accomplished, substitution in hypothyroidism should aim at low normal TSH, to ensure normal T3 levels.     

Effect of treatment of hypothyroidism on the plasma concentrations of neuroactive steroids and homocysteine.

Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.     

Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.     

奥氮平对精神分裂症患者甲状腺素和泌乳素的影响

目的 探讨奥氮平对精神分裂症患者甲状腺素和泌乳素水平的影响.方法 对服用奥氮平治疗的32例精神分裂症患者,于治疗前后检测甲状腺各项生化指标及泌乳素水平,并进行对比分析.结果 治疗后入组被试游离三碘甲状腺原氨酸、游离甲状腺素水平较治疗前显著降低（P＜0.05）,泌乳素水平较治疗前显著升高（P＜0.01）.结论 奥氮平可致精神分裂症患者的甲状腺激素水平下降,泌乳素升高,建议临床应对服用奥氮平患者定期检测甲状腺功能和泌乳素水平.     

原发性甲状腺功能减退症与血脂代谢的相关性研究

目的：探讨不同程度甲状腺功能减退症和病程对血脂的影响,并观察甲状腺功能减退症患者激素替代治疗后血脂谱的动态变化。方法收集甲状腺功能减退症患者97例,亚临床甲状腺功能减退症32例,中度甲状腺功能减退症28例,重度甲状腺功能减退症37例和31例健康体检者。分别在初诊和激素替代治疗1个月后检测各组血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、促甲状腺激素（TSH）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A（ApoA）、载脂蛋白B（ApoB）、脂蛋白（a）[Lp（a）]。通过病史回顾对病程估计的方法确定病程时间。结果不同程度的甲状腺功能减退症对血脂影响不同,重度甲状腺功能减退症组血脂各项均升高,中度甲状腺功能减退症组除TG与HDL-C外均升高,亚甲状腺功能减退症组ApoA与Lp（a）升高。血脂各项与FT3和FT4呈负相关,与TSH呈正相关。甲状腺功能减退症患者激素替代治疗1个月后血脂各项除 Lp（a）外其余基本恢复正常。结论甲状腺功能减退症可引起血脂增高,随甲状腺功能减退症程度加重及病程延长,血脂升高越明显,经激素替代治疗后,甲状腺功能减退症病情好转血脂逐渐恢复,血脂可先于甲状腺功能恢复正常。     

Serum level of the circulating angiogenesis inhibitor endostatin in patients with hyperthyroidism or hypothyroidism

Serum level of endostatin, a natural angiogenesis inhibitor, was measured in 12 patients with hyperthyroidism and 9 patients with hypothyroidism. Control values were obtained from 12 healthy individuals. Hyperthyroidism was shown to be associated with an increased level of endostatin and hypothyroidism with a decreased endostatin level. There was no correlation of serum endostatin with thyroid hormone levels. Endostatin is a fragment of type XVIII collagen, and it is possible that reported changes are related to the effect of thyroid hormones on connective tissue metabolism.     

Pain perception, blood pressure levels, and peripheral benzodiazepine receptors in patients followed for differentiated thyroid carcinoma: a longitudinal study in hypothyroidism and during hormone treatment

BACKGROUND: Elevated blood pressure levels that are associated with hypalgesia and hypothyroidism have major influences on the cardiovascular system. The potential modulation of pain sensitivity by thyroid hormones is largely undetermined. Moreover, a few experimental studies show that peripheral benzodiazepine receptors (PBRs), which may be altered in hypothyroidism, seem to be related with pain perception. METHODS: Dental pain threshold and tolerance were evaluated in 19 patients followed for differentiated thyroid carcinoma (1) in severe short-term hypothyroidism (phase 1) and (2) during thyroid stimulating hormone-suppressive LT4 treatment (phase 2). PBR expression (cytofluorimetric evaluation) on peripheral blood mononuclear cells was also investigated in the 2 phases. RESULTS: Pain perception differed throughout the study, the dental pain threshold was higher in phase 1 (P<0.05) whereas pain tolerance was higher but not significantly (P=0.07). Although the systolic blood pressure was higher during hypothyroidism (P<0.01), no relationship was found between blood pressure changes and pain sensitivity variations. Moreover, the multiple regression analysis showed an independent association of the clinical phase with pain sensitivity (r=-2.61, P=0.029), while accounting for systolic blood pressure. The intensity of PBRs was significantly higher in the first phase of the study (P=0.047) whereas the ratio did not significantly differ. However, no relationship was observed between pain sensitivity and PBRs. DISCUSSION: In conclusion, in athyreotic patients, the pain sensitivity is related to the thyroid status and is independent of the increase in blood pressure induced by thyroid hormone deprivation. The PBRs do not seem to have major influence on pain sensitivity changes in hypothyroidism.     

原发性甲状腺功能减退症并心包积液临床分析

目的 探讨原发性甲状腺功能减退症发生心包积液的临床特点.方法 对38例原发性甲状腺功能减退症患者进行回顾性分析,根据超声心动图检查结果分为合并心包积液组19例与无心包积液组19例.分别对两组患者的临床特征:甲状腺功能、血液系统、肝功能 、血脂水平、心脏彩色多普勒检查等进行两样本t检验.结果 合并心包积液组患者的甲状腺激素(TH)、血红蛋白(HB)、射血分数(EF)、白蛋白(ALB)水平均显著低于无心包积液组(P<0.05).结论 原发性甲状腺功能减退症发生心包积液易合并多系统功能障碍,在甲状腺激素水平极低,及合并贫血、低蛋白血症的时候应行心脏彩色多普勒检查排除心包积液可能.     

阻塞性睡眠呼吸暂停低通气综合征对甲状腺功能的影响

目的 探讨阻塞性睡眠呼吸暂停低通气综合征（OSAHS）对甲状腺功能的影响。方法 回顾性分析2015年1月至2016年2月在四川大学华西医院行整夜睡眠呼吸监测及甲状腺功能检查的400例住院患者,根据呼吸暂停低通气指数（AHI）水平分为非OSAHS组及OSAHS组,其中OSAHS组又进一步分为轻度OSAHS组、中度OSAHS组和重度OSAHS组,比较各组在性别、年龄、体重指数（BMI）、合并甲状腺功能减退、糖尿病或高血压的比例、甲状腺激素水平（TSH、FT3、FT4）及甲状腺相关抗体（TgAb、TPOAb）方面的差异。应用多元Logistic回归对OSAHS与甲状腺功能的关系进行分析。结果 OSAHS组的男性比例、年龄、BMI、合并糖尿病或高血压的比例均高于非OSAHS组（P<0.01）。重度OSAHS组的FT3水平略高于非OSAHS组及轻度OSAHS组（P<0.05）。非OSAHS组的TPOAb阳性率高于OSAHS组(P=0.049)。多元Logistic回归分析显示OSAHS与甲状腺功能不相关。结论 OSAHS可能对甲状腺功能无显著影响。     

男性甲状腺功能亢进及低下患者血清性激素测定分析

目的：分析男性甲状腺功能亢进（甲亢）和甲状腺功能减退（甲减）患者性激素水平的变化及其临床意义。方法选择2013年1～6月来该院诊治并确诊为甲亢及甲减的男性患者,分为甲亢组及甲减组,另选健康志愿者为对照组,采用化学发光方法分别在治疗前及病情缓解分别检测性激素的水平。结果治疗前甲亢组及甲减组的血清促卵泡刺激激素（FS H ）、促黄体生成激素（L H ）水平与对照组比较差异无统计学意义（ P＞0．05）;治疗前甲亢组及甲减组的血清垂体泌乳素（PRL ）、雌二醇（E2）和睾酮（T）水平与对照组比较差异有统计学意义（P＜0．05）。治疗后甲亢组的血清E2水平与对照组比较差异有统计学意义（P＜0．05）。甲亢组血清PRL、E2及T水平治疗前后比较差异有统计学意义（P＜0．05）;甲减组血清PRL、E2及T水平治疗前后比较差异有统计学意义（ P＜0．05）。结论甲状腺激素水平对血清FS H、L H水平影响不明显,主要通过影响性激素PRL、E2及T水平变化,影响性功能等。     

Evaluation of biochemical, hematological, and thyroid function parameters in nondipper and dipper hypertensive patients

AIM OF THE STUDY: In this study we investigated the effects of biochemical, hematologic, and thyroid function parameters on the circadian rhythm of hypertensive patients whose 24-h ambulatory blood pressure was being followed. METHODS: We studied the fasting glucose, urea, creatinine, uric acid, aspartate transaminase, alanine aminotransferase, gamma-glutamyl transferase, total protein, albumin, lipid profiles, sodium, potassium, hemoglobin, white blood cell count, platelet count, mean platelet volume, thyroid stimulating hormone, free thyroid hormone values obtained simultaneously with 24-h ambulatory blood pressure results, as documented in the case records of 470 patients. PATIENTS: Of the patients, 398 were in the nondipper hypertensive group and 72 in the dipper hypertensive group. Differences in serum biochemical, hematologic, and thyroid function parameters were compared between the groups. RESULTS: No statistically meaningful difference was detected between the age, gender, biochemical and hematologic parameters of the two groups. When the two were compared with respect to thyroid function tests, thyroid stimulating hormone levels in the nondipper hypertensive group were significantly higher, while free triiodothyronine and thyroxine levels were significantly lower. CONCLUSIONS: Thyroid function disorders are associated with hypertension. However, there are not enough data on the effects of thyroid hormones particularly on the nighttime blood pressure decrease in hypertensive patients. Although the exact mechanism between low thyroid hormone levels and nondipping hypertension development is not known, relatively low thyroid hormone levels in the nondipper group may be related to the decrease in vein wall compliance, considering the vascular effect of overt hypothyroidism.     

125例女性甲状腺功能减退症患者血清性激素水平检测及分析

目的研究女性甲状腺功能减退症(简称甲减)患者是否存在性激素水平失衡,观察甲状腺激素变化和性激素变化之间的关系。方法采用放射免疫法测定研究对象的睾酮(T)、雌二醇(E2)、促卵泡生成激素(FSH)、促黄体生成激素(LH)、催乳素(PRL)水平,采用硫酸铵沉淀法测定血清性激素结合球蛋白结合容量(SH-BG-BC)。结果 T、E2、SHBG-BC改变差异有统计学意义(P0.01),而FSH、LH、PRL显著升高,差异有统计学意义(P0.01),女性甲减患者性激素E2下降明显,差异有统计学意义(P0.01)。结论女性甲减患者性激素水平紊乱。     

Modulation of in vitro erythropoiesis. Studies with euthyroid and hypothyroid dogs.

The interactions of adrenergic agonists and thyroid hormones on the growth of erythroid colony-forming units were studied in cultures of dog marrow before and after the establishment of hypothyroidism. Erythroid colony growth in cultures form euthyroid dogs was enhanced by isoproterenol and other adrenergic agonists having beta 2-receptor specificity. With hypothyroidism, however, this responsiveness was lost, and sensitivity to alpha-agonists, such as phenylephrine and norepinephrine, was acquired. This alteration in receptor specificity appeared to be dependent upon thyroid hormone and was rapidly reversible. Preincubation of marrow cells from hypothyroid animals with thyroid hormone resulted in the reappearance of responsiveness to beta-adrenergic agonists and the loss of sensitivity to alpha-agonists. These findings are in agreement with previous suggestions that beta-adrenergic receptor activity is modulated by thyroid hormone levels and demonstrate that the specificity of adrenergic modulations of erythropoiesis in culture may accurately reflect the thyroid status of the intact animal.     

Enhanced prolactin secretion in patients with primary hypothyroidism during thyroid replacement

Thyroid hormones are known to exert some influence on prolactin (PRL) secretion indirectly via the hypothalamic dopaminergic system and directly at the level of pituitary gland. In order to study the effect of thyroid hormones on the activity of hypothalamic dopamine neurons, lactotrophs and thyrotrophs, we administered increasing doses of thyroid hormones to patients with primary hypothyroidism, and examined the changes of basal PRL, TSH and PRL responses to a dopamine receptor blocker (sulpiride). Among 24 patients with primary hypothyroidism, hyperprolactinemia was observed in 10 cases (18.0-236 ng/ml, mean +/- S.E. 58.6 +/- 20.0 ng/ml), while elevated TSH levels were observed in all of them (6.6-972 microU/ml, mean +/- S.E. 231.4 +/- 53.9 microU/ml). There was a significant negative relationship between plasma T3 or T4 levels and basal plasma TSH levels (p less than 0.05), whereas a poor correlation was observed between the thyroid hormones and basal plasma PRL levels (r = -0.25, p greater than 0.05). Following the administration of gradually increasing doses of thyroid hormones, plasma PRL showed paradoxical and transient increases, while plasma TSH decreased steadily. Plasma PRL response to sulpiride also became exaggerated during the treatment. The elevated basal PRL level and the enhanced response to sulpiride turned to be within the normal range when the patients became euthyroid by treatment. These results may indicate that thyroid hormones stimulate not only hypothalamic dopaminergic activity, but also the lactotroph activity in a long term hypothyroid state. Regarding the paradoxical elevation of basal PRL, one can postulate that the activation of lactotroph by a small dose of thyroid hormone may be able to overcome the hypothalamic dopaminergic inhibition.     

Influence of thyroid hormone status on mevalonate metabolism in rats.

Mevalonate, an essential intermediate in cholesterol synthesis, is metabolized either to cholesterol or, by the shunt pathway, to CO2. Previous investigations have demonstrated that the kidneys are the chief site of circulating mevalonate metabolism and that sex hormones as well as insulin markedly influence circulating mevalonate metabolism. The present study examined in rats the influence of thyroid hormone status on mevalonate metabolism in vivo and in vitro. L-thyroxine administration increased renal conversion of circulating mevalonate to cholesterol, 41% in the females and 22% in the males. Conversely, hypothyroidism induced by 6 N propyl-2-thiouracil reduced renal conversion of circulatng mevalonate to cholesterol by 45% in females and 27% in males; thyroid hormone replacement in these animals returned cholesterogenesis in the kidneys to supranormal levels. Neither L-thyroxine nor hypothyroidism altered circulating mevalonate conversion to cholesterol in the liver or carcass. In vitro studies confirmed the in vivo observations. Changes in thyroid hormone produced only minor changes in the shunt pathway of mevalonate metabolism. This study demonstrates that the major effect of the thyroid hormone on the metabolism of circulating mevalonate is to alter the conversion of mevalonate to cholesterol, an effect localized solely to the kidneys.     

Hypothyroidism: etiology, diagnosis, and management

Hypothyroidism is the result of inadequate production of thyroid hormone or inadequate action of thyroid hormone in target tissues. Primary hypothyroidism is the principal manifestation of hypothyroidism, but other causes include central deficiency of thyrotropin-releasing hormone or thyroid-stimulating hormone (TSH), or consumptive hypothyroidism from excessive inactivation of thyroid hormone. Subclinical hypothyroidism is present when there is elevated TSH but a normal free thyroxine level. Treatment involves oral administration of exogenous synthetic thyroid hormone. This review presents an update on the etiology and types of hypothyroidism, including subclinical disease; drugs and thyroid function; and diagnosis and treatment of hypothyroidism.     

Association of thyroid dysfunction with vitamin B12, folate and plasma homocysteine levels in the elderly: a population-based study in Sicily.

BACKGROUND: Association of thyroid dysfunction with plasma homocysteine levels and vitamin B(12) has previously been reported. We evaluated these associations in the elderly in San Teodoro, a mountainous village of Sicily. METHODS: Subjects (n=279) aged 60-85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests. RESULTS: Hypothyroidism and/or goiter were two characteristics that were not associated with a significant change in homocysteine when compared with euthyroidism and the absence of goiter. Vitamin B(12) was significantly higher in subjects in the first quartile of the thyroid-stimulating hormone distribution, compared with those in the fourth quartile (371+/-207 vs. 297+/-196 pmol/L, p=0.0121). Homocysteine was significantly higher in the first quartile of the free tri-iodothyronine distribution compared to the third quartile (18.0+/-5.7 vs. 16.0+/-6.2 micromol/L, p=0.0130) and was correlated with log tri-iodothyronine in euthyroid subjects (p=0.0254). In multivariate analysis, homocysteine was associated with vitamin B(12) (p=0.0014), folate (p<0.0001), creatinine (p<0.0001) and age (p<0.0001), but not with either free tri-iodothyronine (p=0.7680), tetra-iodothyronine (p=0.5706) or thyroid-stimulating hormone (p=0.2294). CONCLUSIONS: Our results suggest that the influence of thyroid hormones on homocysteine is much weaker in elderly subjects than in selected patients with hypothyroidism.     

Biochemical markers of bone turnover in patients with thyroid dysfunctions and in euthyroid controls: a cross-sectional study.

Hyperthyroidism is associated with reduced bone mineral density. Conflicting data exist regarding the effects of thyroxine therapy on bone metabolism. The aim of the present study was to assess changes in markers of bone turnover in thyroid dysfunction. A total of 28 patients with overt hyperthyroidism, eight patients with suppressed TSH levels (thyroid hormones within the euthyroid range, no T4 therapy), 25 euthyroid and four hypothyroid patients were included in the present study. Hyperthyroidism resulted in increased bone metabolism, as reflected by increased bone resorption and bone formation parameters. No significant differences in mean levels between patients with TSH supression and those with euthyroidism could be observed; however, a higher frequency of elevated urinary PYD- and DPD excretion rates were noted in patients with TSH suppression. Regression analysis revealed highly significant correlations between bone resorption markers and thyroid parameters, suggesting, that even a mild thyroid hormone excess may lead to an increase in bone resorption. In subjects with suppressed TSH levels and peripheral thyroid hormone levels within the euthyroid range, elevated bone resorption markers point to subclinical hyperthyroidism, if other reasons for an increase in bone turnover rates can be excluded.     

巨泌乳素血症患者血清性激素和甲状腺激素水平研究

目的探讨巨泌乳素血症(M-PRL)在体内产生和集聚的可能机制。方法选取高泌乳素(HPRL)患者50例、MPRL患者50例和健康人群25例分别作为HPRL组、M-PRL组和对照组,采用化学发光法检测3组血清性激素和甲状腺素水平,对检测结果进行统计分析。结果 M-PRL组、HPRL组血清睾酮、性激素结合球蛋白(SHBG)水平均高于对照组,差异有统计学意义(P0.05);M-PRL组、HPRL组血清雌二醇水平低于对照组,差异有统计学意义(P0.05);M-PRL组血清孕酮水平低于对照组,差异有统计学意义(P0.05);M-PRL组血清睾酮、雌二醇、促黄体生成素(LH)、促卵泡生成素(FSH)、SHBG水平和LH/FSH比值与HPRL组比较,差异无统计学意义(P0.05)。结论 M-PRL血症患者体内可能存在一定程度的性腺激素水平异常和自身免疫状态异常。