Thyrotrophin augmentation after commencing thyroxine replacement in primary hypothyroidism

Prospective measurements of serum thyrotrophin and thyroxine concentrations were made in six patients with primary hypothyroidism treated consecutively with an incremental regimen of oral thyroxine. A fall in thyrotrophin occurred over several months, accompanied by a concurrent slow rise in serum thyroxine. Those patients with the highest initial values for thyrotrophin showed the typical curvilinear decline in thyrotrophin, whereas the remaining patients disclosed a transient rise in thyrotrophin for the first 3 months. This paradoxical rise was not associated with depression of cardiac output or glomerular filtration rate. The significance of thyrotrophin augmentation is uncertain, but it may be more common than generally appreciated. It did not occur in those patients with the most severe degrees of thyroid deficiency. Thyroxine exerts a dual action, and augmentation of thyrotrophin may reflect a dominant effect of increased protein synthesis, in contrast to negative feedback inhibition which suppresses thyrotrophin. These opposing actions are in competition at different dose levels of thyroxine, and may contribute not only to augmentation or suppression of thyrotrophin, but also to the curvi-linear pattern of fall. Such variations impair the utility of thyrotrophin as an index of euthyroidism.     

Primary hypothyroidism presenting as a pituitary mass

Pituitary enlargement secondary to primary hypothyroidism is a known but uncommon occurrence, which can be difficult to distinguish on computerized tomography (CT) and magnetic resonance imaging (MRI) from primary pituitary tumors. We describe a 33 year old female who was referred to a neurosurgeon for removal of a pituitary mass. The markedly elevated thyrotrophin stimulating hormone (TSH), absence of clinical features of hyperthyroidism, and low thyroid hormone values led to a diagnosis of pituitary enlargement secondary to primary hypothyroidism. The pituitary gland returned to normal size with thyroxine replacement therapy. Surgery was not indicated.     

Hypothyroidism

Hypothyroidism, due to deficiency of circulating thyroid hormones, is a disease with wide ranging symptoms and signs affecting many systems and presenting to various specialists. Once suspected it can be easily diagnosed by a simple blood test measuring serum thyroxine (T4) and thyroid stimulating hormone (TSH) levels. Treatment of hypothyroidism is by giving levothyroxine orally, and the dose is to be titrated to keep the serum TSH within the normal range. The clinical entity of subclinical hypothyroidism, characterised by normal T4 and elevated TSH is being diagnosed more frequently, and is emerging as a new indication for thyroxine therapy.     

Congenital hypothyroidism from complete iodide transport defect: long-term evolution with iodide treatment

Hypothyroidism from iodide transport deficiency is a rare disease, especially when found in two affected siblings. Treatment with high doses of iodide has been recommended, but no long term results have been reported. Two siblings with congenital hypothyroidism due to total failure to transport iodide have been followed up during twelve and a half years of treatment with oral potassium iodide. Iodine doses varied between 10.3 and 22 mg/day, and serum total iodine concentrations between 100 and 210 micrograms/dl. Total triiodothyronine (T3), thyroxine (T4) and free T4 were in the normal range during the time of study. Basal thyroid stimulating hormones (TSH) and maximum TSH response to thyrotrophin releasing hormone (TRH) were also in the range of normal values. These data along with clinical findings confirmed the potential usefulness of iodine in hypothyroidism due to complete iodide transport defect.     

亚临床甲状腺疾病与稽留流产的相关性研究

目的:分析亚临床甲状腺疾病与稽留流产相关性,降低稽留流产率.方法:收集稽留流产病人71例为观察组,正常妊娠孕妇80名为对照组,检测其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)、甲状腺球蛋白抗体(TGAb)及甲状腺微粒体抗体(TMAb)水平并分组进行比较,随访妊娠结局.结果:观察组FT3、FT4、TSH、TGAb、TMAb水平与对照组差异均无统计学意义(P>0.05).观察组亚临床甲状腺疾病患病率高于对照组(P<0.01),主要为亚临床甲状腺功能减退(TSH增高型),甲状腺自身抗体及亚临床甲状腺功能亢进患病情况无明显差异(P>0.05).结论:亚临床甲状腺功能减退(TSH增高型)与稽留流产率有一定关系,亚临床甲状腺功能亢进及甲状腺自身抗体与稽留流产均无明显关系;亚临床甲状腺疾病对稽留流产的影响多作用于早孕期.     

Postoperative pituitary hormonal disturbances and hormone replacement therapy time and dosage in children with craniopharyngiomas

Background The proliferative activity and penetration into the hypothalamic structures in children craniopharyngiomas （CP） often make radical resection difficult. Therefore, complete resection of CP often results in permanent multiple pituitary hormone deficiency （MPHD）. This study aimed to elucidate the postoperative pituitary hormonal disturbances, and hormone replacement therapy （HRT） time and dosage in children with CP.
Methods Twenty patients with growth retardation and CP after resection, comprising 14 boys and 6 girls, with a mean age of （10.63±3.18） years （Group A） and 10 male patients of group A aged 〉10 years （Group B） were entolled. Thirty age-, sex- and Tanner stage-matched normal children （control Group A）, and 44 male older children 〉10 years （control Group B） served as controls. The serum concentrations of insulin-like growth factor-1 （IGF-1）, growth hormone （GH）, free thyroxine （FT4）, thyroid-stimulating hormone （TSH）, adrenocorticortropic hormone （ACTH）, cortisol （COR）, follicle stimulating hormone （FSH）, luteinizing hormone （LH）, prolactin （PRL）, testosterone （T） and estradiol （E2） were measured in the CP patients after resection and in controls. The appropriate time and dosage of HRT were investigated. Linear correlation analysis was made between levothyroxine （L-T4） dosage and primary FT4 in CP patients after resection.
Results All cases had MPHD. The serum peak GH, IGF-1, FT4 and COR levels of Group A were significantly lower than that of the control Group A. The serum IGF-1 concentration increased to the normal level after 3 months of rhGH therapy; the serum FSH, LH, and T levels were significantly decreased （P 〈0.001）; however, E2 and PRL were significantly increased （P 〈0.001） in Group B compared with the control Group B; 18 cases were found to have central diabetes insipidus （DI） by water deprivation test and MRI. There was a significant negative linear regression （r=-0.8, P 〈0.001     

The effective evaluation of thyroid status in patients on phenytoin, carbamazepine or sodium valproate attending an epilepsy clinic

To assess the most efficient means of monitoring thyroid status in an epilepsy clinic, total thyroxine (T4), free thyroxine stimulating hormone (TSH) were measured in 71 adult patients treated long-term with either phenytoin (DPH), carbamazepine (CBZ) or sodium valproate (VAL). Twenty-seven patients with one or more abnormal thyroid hormone results were further investigated by a thyrotrophin releasing hormone (TRH) test and clinical assessment. T4 was found to be normal in 85% on VAL, 40% on CBZ and 39% on DPH. FT4 was normal in more patients, namely 95% on VAL, 70% on CBZ and 65% on DPH. The TRH tests indicated that FT4 was the most efficient screening test for hypothyroidism in this epileptic population. We estimate that the use of FT4 alone as a screening test would have reduced by 60% the number of TRH tests required.     

左甲状腺素钠联合甲状腺片对甲减患者甲状腺激素变化的影响

目的：研究左甲状腺素钠联合甲状腺片对甲减患者甲状腺激素变化的影响。方法整群选取从2013年5月—2016年1月,于该院进行诊治的甲减患者86例。以数字法随机分为观察组和对照组各43例。给予两组患者甲状腺片治疗,观察组在此基础上加用左甲状腺素钠。对比两组疗效以及促甲状腺激素(TSH)、总胆固醇(CHOL)、三酰甘油(TG)、血清游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)水平。结果观察组显效人数占比以及总有效分别为65.12%、95.35%,显著高于对照组的41.86%、79.07%。观察组TSH、CHOL、TG水平分别显著低于对照组;而FT3、FT4水平分别明显高于对照组,差异均有统计学意义(P<0.05)。结论左甲状腺素钠联合甲状腺片临床治疗甲减患者疗效显著,能有效缓解患者痛苦,促进患者早日康复,安全性好,值得临床推广应用。     

EFFECT OF THYROID HORMONE DOSAGE ON THYROID FUNCTION TESTS IN T4-REPLACED HYPOTHYROID PATIENTS

To examine the relative importance of serum thyroxine (T4), free thyroxine (fT4) and triiodo thyronine (T3) in monitoring adequate T4 dose in patients on T4-replacement therapy, the effect of T4 dose on total T4, fT4 and T3, basal thyroid stimulat- ing hormone (TSH) and TSH-response to thyrotropin releasing hormone (TRI'I) were investigated in 33 patients taking T4 doses of 50-200\µg/day. The T4- treated patients had highly elevated mean T4 (total and free) and lower basal TSH levels compared to the mean values in normal subjects. But serum T3 was not significantly different. The patients on T4 doses greater than 150Ug/day frequently had more suppressed TSH response tol TRH than those on T4 doses less than 150µg/day. Total T4 and T4, but not serum T3 levels, cerrelated significantly with T4 dosage. Changes in T4 dosage led to concomi tant changes in total T4 and fT4 and inverse changes in TSH-response to TRH. The study also revealed a high incidence (33%) of elevated serum fT4 (hyperthyroxinemia) dLtring therapy. The hyperthyroxinemic group was characterised by clevated serum T4 (total ancl free), T3 and T4 dose, and suppressed TSH-response to TRH compared to the T4-treated group with normal serum T4 Ievels. These findings may be indicative of excessive T4 treatment iri these patients and suggest serum T4 may be more useful than T3 in monitoring T4 dosage in T4-replacement therapy. The discrepancy between normal serum T4 levels and TSH-response to TRH may reflect hetero- geneity in returning normal function of the pituitary- thyroid axis. Clearly, measurement of TSH or TRH test can ~ot be used alone in assessing thyroid status iki these patients, particularly when serum T4 is in normal'range.     

Graves' ophthalmopathy and subclinical hypothyroidism: diagnostic value of the thyrotropin releasing hormone test.

Five patients with Graves' ophthalmopathy and no previously documented clinical or laboratory evidence of hyperthyroidism were studied. Their serum levels of thyroxine and triiodothyronine (T3) and their T3 uptake were normal. Although the baseline serum level of thyrotropin (TSH) was normal in two patients, it was increased on the other three, and when TSH releasing hormone (TRH) was administered the T3 response was impaired in three patients and the TSH response was exaggerated in all five. These findings facilitated the diagnosis of subclinical hypothyroidism and distinguished the patients from those with Graves' ophthalmopathy and normal thyroid function or subclinical hyperthyroidism. Thyroid antibodies were detected in the serum of four of the five patients, suggesting the coexistence of chronic autoimmune thyroiditis; this disorder could account in part for the subclinical hypothyroidism, which was even present in the two patients in whom thyroid-stimulating immunoglobulin was found in the serum. These observations indicate the value of a TRH stimulation test in detecting subclinical hypothyroidism in patients with Graves' ophthalmopathy who appear from clinical and routine laboratory studies to have normal thyroid function but could have normal function or subclinical hyperthyroidism.     

Total and free thyroid hormone concentrations in patients receiving maintenance replacement treatment with thyroxine

Total and free serum concentrations of thyroxine and triiodothyronine were measured in 122 subjects with hypothyroidism who were clinically well while receiving conventional replacement treatment with thyroxine. In a third of patients concentrations of total and free thyroxine were raised, often considerably; nevertheless concentrations of total and free triiodothyronine were usually normal. Though significant correlations were obtained between total triiodothyronine concentrations and total thyroxine concentrations (p less than 0.001) and between the triiodothyronine concentrations and free thyroxine concentrations (p less than 0.001) the slope of the line of the regression equation describing these correlations was small, hence large increases in both total and free thyroxine concentrations were accompanied by only modest increases in total and free triiodothyronine concentrations. The presence of total or free thyroxine concentrations above normal in patients taking thyroxine therefore are not necessarily of clinical consequence. In the assessment of adequacy of replacement treatment with thyroxine the most logical combination of in vitro thyroid function test results may be a normal thyrotrophin concentration and normal free triiodothyronine concentration.     

Primary hypothyroidism with paradoxically elevated plasma thyroxine due to thyroxine-binding antibody

Investigation of an elderly patient with clinical hypothyroidism revealed a low serum triiodothyronine (T3) but markedly raised levels of total thyroxine (TT4) and free thyroxine (fT4) when measured by radio-immunoassay (RIA). Primary hypothyroidism was suggested by an elevated basal thyroid stimulating hormone (TSH) and confirmed by a low fT4 when measured by a commercial microencapsulated antibody method. The paradoxically elevated levels of fT4 and TT4 were due to the presence of an antibody which specifically bound T4 and grossly interfered with the RIA thus complicating the diagnosis and later the assessment of replacement therapy. The sensitive immunoradiometric TSH assay proved of value in resolving these problems.     

甲状腺素片联合左甲状腺素钠片治疗甲减的疗效观察

目的探究甲减患者采用甲状腺素片联合左甲状腺素钠片治疗的疗效。方法选取2017年5月至2019年5月于本院诊治的100例甲减患者,按随机数字表法分为两组,各50例。对照组采用左甲状腺素钠片治疗,观察组在对照组基础上联合甲状腺素片治疗,比较两组疗效及甲状腺功能。结果治疗后,观察组总有效率(86.00%)高于对照组(64.00%),差异有统计学意义(P<0.05);两组治疗后总甲状腺素(TT4)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平均高于治疗前,而促甲状腺激素(TSH)水平低于治疗前,且观察组TT4、FT3、FT4水平高于对照组,TSH水平低于对照组,差异有统计学意义(P<0.05)。结论甲减患者采用甲状腺素片联合左甲状腺素钠片治疗的效果较好,有利于改善患者的甲状腺功能。     

Normal thyrotrophin response to intravenous thyrotrophin releasing hormone administration: the best index of optimal L-thyroxine therapy in primary hypothyroidism

Normalization of basal thyrotrophin (TSH) level is used as the endpoint in L-thyroxine (L-T4) therapy of primary hypothyroidism. However, several reports have questioned the reliability of this index because of seasonal variation of TSH. Therefore, we studied 85 consecutive patients with primary hypothyroidism over a period of 3.5 y. In these patients, TSH response (delta TSH) to intravenous thyrotrophin releasing hormone (TRH) administration was examined when basal TSH was normalized with L-T4 therapy. Eight patients showed a blunted response (delta TSH less than 5 microU), whereas 27 patients demonstrated an exaggerated response (delta TSH greater than 25 microU). Thus, 42% of patients were apparently on inappropriate L-T4 dosage. These abnormal TSH responses normalized on adjusting the L-T4 dosage alone; prolonged therapy with the same dose failed to normalize TSH responses. Minor seasonal variations of basal TSH were observed in 30% of patients. However, TSH response to TRH remained normal. Hence, no adjustment of L-thyroxine dose was required. This study, therefore, demonstrates that normalization of TSH response to TRH administration rather than basal TSH may be the best index of adequate L-thyroxine therapy in primary hypothyroidism.     

Management of the unexpected result: compensated hypothyroidism.

The combination of elevated serum thyrotropin and normal serum thyroxine is called compensated or subclinical hypothyroidism. This most commonly represents clinically silent autoimmune thyroiditis. Whether this condition warrants treatment or simply observation is still debated. The risk of developing overt hypothyroidism is high in females with elevated thyrotropin above 10 mU/l and/or positive thyroid microsomal antibodies. Males are also at high risk of progression towards overt hypothyroidism, regardless of antibody status or degree of thyrotropin elevation. We advise routine treatment of only those at high risk of developing overt hypothyroidism.     

Impaired thyrotrophin secretion following the administration of thyrotrophin-releasing hormone in type II diabetes mellitus

Serum thyrotrophin has been measured before and after the intravenous administration of 200 micrograms of thyrotrophin-releasing hormone in 91 white subjects (33 stable diabetic patients and 58 healthy controls), none of whom had any clinical evidence of thyroid or pituitary dysfunction. Seven of the diabetic subjects failed to achieve a rise of serum thyrotrophin of greater than 2 mU/l above basal concentrations, as compared with only one of the control subjects (P = 0.006). The difference in response between diabetics and controls was confined to patients with Type II (non-insulin-dependent) diabetes: thus 5 of 13 Type II patients and 2 of 20 Type I (insulin-dependent) patients failed to show a normal response to thyrotrophin releasing hormone injection. No significant effect of glycaemic control on thyrotrophin responses was noted. These results suggest that Type II diabetes mellitus may be a cause of impaired thyrotrophin secretion in patients with no clinical evidence of pituitary disease. The mechanism for this impaired pituitary hormone release remains to be clarified.     

Relevance of increased serum thyroxine concentrations associated with normal serum triiodothyronine values in hypothyroid patients receiving thyroxine: a case for "tissue thyrotoxicosis"

Fifteen patients receiving standard thyroxine replacement therapy (100-200 micrograms daily) for primary hypothyroidism and who had persistently raised free thyroxine concentrations in their serum were investigated to see whether the dose being given was too high. In addition to the usual thyroid hormone assays systolic time intervals (which indicate left ventricular contractility) were calculated as accurate reflectors of tissue thyroid activity. All patients showed the expected increased free and total thyroxine concentrations; but mean total and free concentrations of triiodothyronine were normal, while reverse triiodothyronine values were raised. Mean systolic time intervals were significantly reduced as compared with normal and fell within the thyrotoxic range. Seven patients subsequently had their doses of thyroxine reduced by 50 micrograms daily and were reinvestigated one month later. All showed significant falls in circulating thyroxine and triiodothyronine concentrations and an increase in mean systolic time intervals to the normal range. In patients receiving thyroxine replacement therapy for primary hypothyroidism a raised serum thyroxine concentration may indicate tissue thyrotoxicosis and should prompt a reduction of the thyroxine dose.     

The effects of amiodarone on thyroid function.

The effects of amiodarone on thyroid function tests in 100 patients treated for 6 weeks to 8 years are reported. One patient became thyrotoxic and 10 developed latent or overt hypothyroidism. Twenty-five patients remained clinically euthyroid throughout, but had free thyroxine indices above the normal range. In these patients with apparently anomalous results, total tri-iodothyronine was normal in 19 cases and low in 1; conversely, free thyroxine was high in all 17 cases in which it was measured. Thyrotrophin releasing hormone (TRH) tests were abnormal in 4 of the 13 patients who had the test. Reverse tri-iodothyronine was significantly raised after 2 weeks amiodarone in 5 healthy subjects, but an equivalent amount of iodine in 9 healthy individuals did not significantly affect any of these tests. We believe that these changes are due in part to inhibition of peripheral conversion of thyroxine to tri-iodothyronine with diversion to reversed tri-iodothyronine. Thyroid function tests should be checked once or twice a year in all patients on maintenance amiodarone. Tests indicating hypothyroidism are likely to be clinically relevant, whereas levels of thyroxine suggesting thyrotoxicosis may be misleading and do not usually imply the need to discontinue treatment with the drug.     

Abnormalities of thyroid function tests in hospital inpatients

Results of thyroid function tests were analysed in 199 clinically euthyroid inpatients with normal serum thyroid stimulating hormone values. Serum total triiodothyronine was less than 1.25 nmol/l in 61.8% of samples, free triiodothyronine less than 3.9 pmol/l in 57.8%, total thyroxine less than 63 nmol/l in 21.1% and free thyroxine less than 9.5 pmol/l in 17.6%. In contrast, thyroxine binding globulin ratio was below normal (less than 5) in only 5 samples. A significant positive correlation (P less than 0.001) of serum free thyroxine with total thyroxine, thyroxine/thyroxine binding globulin ratio and free triiodothyronine was present as well as a significant negative correlation (P less than 0.001) with serum thyroid stimulating hormone. There was no correlation of free thyroxine measurements with serum albumin or non-esterified fatty acid concentrations. Although serum free thyroxine is low in a number of patients with non-thyroidal illnesses, this does not appear to be due to a rise in non-esterified fatty acids or a fall in albumin as has been proposed. Serum thyroid stimulating hormone measurements are essential to confirm the diagnosis of hypothyroidism in such subjects.     

Thyroid function in thalassaemia major

INTRODUCTION: Short stature is common in thalassaemia major. Hypothyroidism resulting from haemosiderosis has been implicated, but this complication has not been investigated in Sri Lanka. OBJECTIVES: To estimate the thyroid hormone level of patients with thalassaemia major and correlate height with age, iron status and thyroid hormone level. SETTING: University Unit, Lady Ridgeway Hospital, Colombo. DESIGN: A cross-sectional comparative study. METHODS: 33 patients with thalassemia major (19 males) aged 2 years 6 months to 23 years were studied. 21 healthy age and sex matched subjects from the same neighbourhood as the patients served as controls. Anthropometric measurements, skeletal maturity, serum ferritin and thyroid hormone levels were estimated. RESULTS: The height centiles and height standard deviation scores (SDS) were significantly lower in the patient group. Skeletal maturation was delayed by more than 1 year in 69% of patients. Undernutrition was not seen. The height SDS showed significant reduction with age (r = -0.5, 95% confidence limit -0.72 to -0.18) and with elevated serum ferritin levels (r = -0.8, 95% confidence limit = -0.9 to 0.62). Serum ferritin levels were elevated in the entire patient group with 70% being heavily iron overloaded (serum ferritin > 7000 ng/ml). The thyroxine (T4) levels were within the normal range in all 33 patients. The TSH levels were normal in 32 patients. The patient too had a normal T4 level. The control group had TSH levels comparable with the patients. CONCLUSION: Hypothyroidism was not present in our iron overloaded thalassaemic patients. The thyroid hormone levels were similar in patients with mild and heavy iron overload. We conclude that routine surveillance for hypothyroidism is unnecessary in thalassaemia major. Other causes for delayed skeletal maturation and short stature need investigation.