垂体促甲状腺激素腺瘤中SSTR表达谱及全数字切片自动图像分析的探索性研究

  目的  探索垂体促甲状腺激素（thyroid stimulating hormone,TSH）腺瘤中生长抑素受体（somatostatin receptor,SSTR）的表达以及全数字切片自动图像分析技术的应用。  方法  分析2013年1月至2019年12月北京协和医院的37例垂体TSH腺瘤的石蜡包埋组织标本及临床病理资料,利用各型SSTR1-SSTR5抗体进行免疫组织化学染色,分别进行人工判读和全数字切片自动图像分析,比较各型SSTR表达与性别、年龄、肿瘤大小、Ki-67指数以及侵袭的相关性,并对比人工判读和软件自动分析的一致性。   结果  垂体TSH腺瘤中SSTR1、SSTR2、SSTR4和SSTR5多为2分和3分表达,其中3分占比均超过50.0%（4型SSTR占比依次分别为59.5%、78.4%、64.9%和56.8%）。SSTR1表达与侵袭呈明显负相关（人工r=-0.417,P=0.010;软件r=-0.406,P=0.013）,并与SSTR2表达具有显著相关性（人工r=0.420,P=0.010;软件r=0.338,P=0.040）。各型SSTR表达的人工判读与图像自动分析结果均显示了较好的一致性。  结论  垂体TSH腺瘤肿瘤组织中SSTR1、SSTR2、SSTR4和SSTR5均有较高水平的表达,利用基于数字化全切片的图像自动分析技术可获得与病理医师人工判读相近的评估效果。     

Hypothyroidism and levothyroxine therapy following bariatric surgery: a systematic review,meta-analysis,network meta-analysis,and meta-regression

BackgroundMany health benefits of bariatric surgery are known and well-studied, but there is scarce data on the benefits of bariatric surgery on the thyroid function.ObjectiveWe aimed to make a meta-analysis regarding the impact of bariatric surgery on thyroid-stimulating hormone (TSH) levels, levothyroxine dose, and the status of subclinical hypothyroidism.SettingSystematic review and meta-analysis.MethodsPubMed, EMBASE, and Cochrane Library were searched up to December 2020 for relevant clinical studies. Random-effects model was used to pool results. Network meta-analysis was performed, incorporating direct and indirect comparisons among different types of bariatric surgery. Meta-regression analysis was performed to evaluate the impact of moderator variables on TSH levels and required levothyroxine dose after surgery. We followed the PRISMA guidelines for data selection and extraction. PROSPERO registry number: CRD42018105739.ResultsA total of 28 studies involving 1284 patients were included. There was a statistically significant decrease in TSH levels after bariatric surgery (mean difference = ?1.66 mU/L, 95%CI [?2.29, ?1.03], P < .0001). In meta-regression analysis, we found that the following moderator variables: length of follow-up, mean age, baseline TSH, and preoperative thyroid function, could explain 1%, 43%, 68%, and 88% of the between-study variance, respectively. Furthermore, subclinical hypothyroidism was completely resolved in 87% of patients following bariatric surgery. In addition, there was a statistically significant decrease of levothyroxine dose in frank hypothyroid patients following bariatric surgery (mean difference = ?13.20 mcg/d, 95%CI [?19.69, ?6.71]). In network meta-analysis, we found that discontinuing or decreasing levothyroxine dose was significant following Roux-en-Y gastric bypass, 1 anastomosis gastric bypass, and sleeve gastrectomy, (OR = 31.02, 95%CI [10.34, 93.08]), (OR = 41.73, 95%CI [2.04, 854.69]), (OR = 104.03, 95%CI [35.79, 302.38]), respectively.ConclusionsBased on our meta-analysis, bariatric surgery is associated with the resolution of subclinical hypothyroidism, a decrease in TSH levels, and a decrease in levothyroxine dose.     

临沂市新生儿脐带血促甲状腺激素水平的调查

目的了解临沂市新生儿碘营养状况.方法于2002年3～5月在全市范围按PPS(组群抽样)法抽取30个点,检测新生儿脐带全血促甲状腺激素(TSH)水平.结果检测新生儿脐带血862份,TSH中位数为3.535 mU/L,＞5 mU/L的脐血样品数占31.7%,与1995年(41.4%)相比有所下降(P＜0.05),但仍远高于"新生儿TSH＞5 mU/L的比例＜3%"的碘缺乏病消除标准.同时发现新生儿TSH水平与8～10岁儿童甲状腺肿大率及尿碘水平存在着严重分离现象.结论临沂市新生儿碘营养状况有所改善,但仍存在碘营养不足.建议加强对孕妇等待需人群的补碘工作,并尽快研究出与国际接轨的新生儿脐带血TSH切点值.     

Hormonal changes induced by a partial opiate antagonist,nalorphine. Evaluation of PRL,GH, TSH,LH, FSH and cortisol secretion

Summary The effects of nalorphine 5 mg i. m., a partial opiate antagonist, on circulating levels of PRL, GH, TSH, LH, FSH and cortisol were studied in six healthy men. Nalorphine produced a prompt and sharp increase in serum PRL and a small, delayed rise in serum GH. Serum LH and cortisol decreased after drug administration and no change in serum FSH and TSH was observed. These findings are discussed and a possible site of action of nalorphine is suggested.     

First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome

Purpose: Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome.

Materials and methods: Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery.

Results: Four thousand five hundred and four women were included in the final analysis – 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500?g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0–3.28 for TSH 2.5–4.0 mIU/L and OR 2.33, 95% CI 1.11–4.42 for those with TSH?>?4 4.0 mIU/L).

Conclusions: Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome – low birth weight and placental abruption – although this needs to be further explored.     

Thyroid status in senile dementia of the Alzheimer type (SDAT)

Thyroid function was investigated in a group of 21 patients with severe senile dementia of the Alzheimer type (SDAT) and in a group of 17 age and sex matched normal controls. Free thyroid hormone levels (triiodothyronine (T3) and thyroxine (T4) were measured, as were also the thyrotrophin (TSH), prolactin (PRL) and growth hormone (GH) responses to thyrotrophin releasing hormone (TRH)). When compared to controls, patients demonstrated a significantly lower free T3 value (but not free T4), a blunted TSH response to TRH, slightly elevated basal PRL and GH values and a small GH response to TRH. However, all differences were small in biological terms and were within the laboratory's normal range. This emphasizes the relative normality of neuroendocrine function, particularly thyroid status, in SDAT.     

Effect of flunarizine on pituitary secretion by healthy men and in woman with migraine

Summary Flunarizine is widely used in the prophylaxis of migraine. It is both a calcium blocker and a histamine antagonist at H₁-receptors and either of these effects could alter hormonal secretion. The effect of administration of flunarizine to 8 women with common migraine on pituitary secretion has been studied. The dopamine antagonist domperidone (10 mg) and gonadotropin releasing hormone (100 µg) were injected iv before and after one month of flunarizine therapy (10 mg orally at bed-time).The basal prolactin level was significantly increased by the drug, and the peak induced by domperidone stimulation was reduced. Basal TSH concentrations were not affected, but the increase after domperidone was blunted.After 90 days of therapy there were no significant differences from the baseline concentration. Neither basal nor gonadotropin releasing hormone — stimulated secretion of FSH and LH were affected by flunarizine. Twelve healthy men were given placebo and flunarizine (10 mg at bedtime) for 5 days in single-blind fashion. Flunarizine caused a significant increase in prolactin and TSH with no effect on basal gonadotropin and thyroid hormone levels.These results can be accounted for by the calcium blocking effect of the drug, although weak interference with dopaminergic transmission is a further possibility explanation.     

自主性高功能性甲状腺腺瘤的外科治疗

目的探讨自主性高功能性甲状腺腺瘤的病因及外科治疗方法。方法回顾性分析10例自主性高功能性甲状腺腺瘤患者的临床资料。结果10例患者均无喉返神经、喉上神经损伤症状，无甲状腺危象发生结论术式应选择腺叶次全或全切除术     

The Response to TRH, LH-RH, Metyrapone and Vasopressin in Patients with Hypothalamo-Pituitary Disorders

Abstract. The effects of slow intravenous infusion of synthetic TRH on serum TSH and of synthetic LH-RH on serum LH measured by radioimmunoassay were studied in healthy persons and in 36 cases with sellar tumours and other hypo-thalamo-pituitary disorders. The results were also compared with the responses to oral metyrapone and intravenous infusion of lysine-8-vasopressin, as tests for the hypothalamo-pituitary-adrenal regulation. 200 μ g of TRH was found to give a mean increase of serum TSH of +10.4 μ/ml in eight males and of +15.7 μ/ml in nine females. LH-RH infusion was found to give a mean increase of serum LH of -f-1.78 ng/ml in six young males. The TRH test gave a pathologically low response in one out of nine patients with an intrasellar tumour. On the other hand in patients with a craniopharyngioma, which usually causes more pronounced pituitary destruction, the response was pathologically low in five out of six cases. A normal response to TRH was obtained in seven out of nine patients with disorders mainly affecting the hypothalamus. When twelve patients with pituitary adenomas were tested post-surgery six patients gave a pathologically low TRH response. The response to LH-RH was pathologically low in five out of eight cases with a pathologically low TRH response and normal in six out of six cases with a normal TRH response. However, there was a poor correlation between the results of these two tests and the vasopressin and metyrapone administration. This difference may be explained by the direct effect of the releasing hormones on the pituitary and the need for a certain hypothalamic function to obtain a response to the vasopressin and metyrapone tests.     

Pituitary tsh response to TRH: Interrelationships with gonadal activity

Summary A TSH radioimmunoassay is described, which was used to investigate the behaviour of the TSH pituitary response (as measured by the secretory area) to TRH in groups of subjects of both sexes and different phases of gonadal activity. It is concluded that the TSH pituitary response is in no way affected by physiological variations in the plasma gonadal hormones. This independent behaviour of the TSH response, uninfluenced by gonadal activity, was apparently confirmed by the results in some pathological conditions (ovarian agenesis and primary male hypogonadism of various types) characterized by very low plasma levels of gonadal hormones.