Thyroxine Substitution Therapy Research Articles

CASE STUDY EFFECTIVNESS OF AMYODARON USE IN PATIENTS WITH SUPRAVENTRICULAR TACHYCARDIA AND HYPOTHYROIDISM


 
 
 A woman, 53 years of age, with recurrent supraventricular tachycardia (SVT) with hypothyroidism was thought to be associated with amiodarone use. Patients repeatedly get amiodarone for their arrhythmias, where amiodarone has a broad antiarrhythmic effect making it effective for the management of SVT. In addition, the low inotropic properties of amiodarone are low, making amiodarone the drug of choice in patients with heart failure. However, repeated use of amiodarone can cause many side effects, one of which is amiodarone induced hypothyroidism (AIH). Patients are given thyroxine hormone substitution therapy during the use of amiodarone and the response to the therapy given is quite good, so the patient has a good prognosis.
 
 

Pituitary tumorous hyperplasia due to primary hypothyroidism

BackgroundTo study the diagnostic and therapeutic features of pituitary tumorous hyperplasia due to primary hypothyroidism.MethodsFifteen patients with pituitary tumorous hyperplasia were studied in clinical manifestation, pathologic, endocrinological, radiographic and therapeutic features retrospectively.ResultsAll of these patients suffered from primary hypothyroidism. Magnetic resonance imaging (MRI) scanning found that there were masses in the sellar region with equal T1 and little longer T2 signal, and which could be obviously enhanced by gadolinium EDTA injection. Diameters of these masses were between 1.1 and 2.5 cm. Thyroxine substitution therapy was ordered. Four months later, MRI scanning found that the masses disappeared and only normal pituitary gland left. Plasma thyroxine, thyroid-stimulating hormone (TSH), and prolactin (PRL) levels dropped to their normal ranges.ConclusionsThyroxine substitution therapy was the first choice of pituitary tumorous hyperplasia due to primary hypothyroidism. If they are followed by TSH adenoma, or the optic chiasma was pressed by the enlarged pituitary, transsphenoidal microsurgery could be applied.

Dyslipidemia in subclinical hypothyroidism and the effect of thyroxine on lipid profile

Introduction:Subclinical hypothyroidism (SH) has a prevalence between 4% and 10.5% in various studies. The burden of SH in India is expected to increase with increasing iodine sufficiency. Studies have shown conflicting results concerning not only the degree of lipid changes in SH but also the effect of thyroxine substitution therapy. Indian studies on dyslipidemia in SH and the effect of thyroxine on lipid profile are currently lacking.Aims and Objectives:(1) To assess the association of SH and lipid profile. (2) To quantify the effect of thyroxine treatment on lipid profile.Materials and Methods:About 54 patients who were detected to have SH were compared with 56 healthy controls. Thyroid stimulating hormone (TSH), free T3, free T4, anti thyroperoxidase (TPO) antibodies, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, Very low density lipoprotein (VLDL) cholesterol, serum triglycerides were measured in all the patients after an overnight fast. Selected patients were started on thyroxine replacement. Twenty-one patients were followed up after 3 months with a repeat lipid profile.Results:Mean total cholesterol and mean LDL levels were significantly higher in SH compared to controls, but there was no statistically significant difference in the mean HDL, VLDL, and triglyceride levels. There was a significant reduction in mean T. cholesterol, mean LDL, mean VLDL, and mean triglyceride levels after treatment with thyroxine, while there was no significant difference among the mean HDL levels.Conclusion:Dyslipidemia is more common in SH compared to controls. There is a TSH dependent increase in cholesterol, LDL, VLDL, and triglyceride levels. Achieving euthyroid status with thyroxine has a favourable effect on lipid profile.

Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects

Thyroid hormones regulate the renal hemodynamics and basal metabolic rate of most cells. This hospital-based case-control study was done to evaluate the changes in biochemical markers of liver and kidney function in hypothyroid subjects before and after treatment. The study included 176 subjects randomly selected from Thyroid clinics. Serum T(3), T(4), TSH, Liver and Kidney Function tests were analysed using standard kits. Forty-six hypothyroid patients were re-evaluated 6 weeks after thyroxine substitution therapy. Hypothyroid subjects (n=80) showed significantly raised serum creatinine and uric acid levels as compared to euthyroid subjects (n=96). After 6 weeks of thyroxine replacement, serum creatinine and uric acid decreased significantly and were comparable to euthyroid group. A positive correlation of ALT, AST, uric acid, protein and albumin with TSH levels (p<0.05) and negative correlation of serum T(4) levels with ALT, AST, proteins (p<0.05) was observed in the hypothyroid group. Hypothyroidism results in reversible impairment of hepatorenal function.

Results and follow-up in eleven MEN 2A gene carriers after prophylactic thyroidectomy

In 11 MEN 2A gene carriers prophylactic thyroidectomy was carried out between the age of 4 to 17 years. All gene carriers had pathological basal and/or pentagastrin stimulated serum calcitonin levels. On histological examination in five patients C-cell hyperplasia (CCH) and in 6 patients medullary microcarcinoma (< 1 cm, mostly multifocally) was shown. No patient had lymph node involvement. There was no recurrent laryngeal nerve damage in these 11 patients and no permanent hypoparathyroidism. After prophylactic thyroidectomy all 11 patients were cured, they showed normal basal and pentagastrin stimulated calcitonin levels. In the follow-up (mean 19 months) under thyroxine substitution therapy in 9 of these 11 patients TSH was at least at one examination out of the normal range. In 2 patients TSH was suppressed, in 1 of these FT3 was slightly elevated. In 7 patients TSH was elevated between 4.9 to 147 microU/ml. The application of genetic testing is save concerning diagnostic accuracy. If prophylactic thyroidectomy is done at early ages cure rate is 100%. Despite this encouraging results thyroxine substitution therapy in the follow-up carries some problems concerning optimal dosage and non-compliance. Therefore TSH has to be estimated in the follow-up every 3 months.

Unique alterations of thyroid function parameters after i.v. administration of alkylating drugs (cyclophosphamide and ifosfamide).

Alkylating drugs (cyclophosphamide and ifosfamide) have been in clinical use for the treatment of malignant diseases in the past. They are most useful anticancer agents and cyclophosphamide is also widely used for its immunosuppressive properties. However the effect of alkylating drugs on thyroid hormone parameters have not been evaluated so far. Three groups of patients were prospectively evaluated: Group I: 15 patients with Wegener's granulomatosis and 4 patients with severe scleritis received a single dose cyclophosphamide (15 mg/kg bw/day) and 250 mg prednisone i.v. Group II: 9 patients with malignant lymphomas were treated according to the IMVP 16-protocol. Patients received daily ifosfamide 1000 mg/m2 from day 0 to 4 and vepesid from day 0 to 2. Patients did not receive corticosteroids additionally. Group III: 6 patients with a relapse of malignant lymphomas received ifosfamide 1.500 mg/m2/day from day 0 to 4 i.v. and dexamethasone 40 mg/m2 as well as ara-c and etoposid. All patients received mesna to prevent hemorrhagic cystitis and odansetran or metoclopramide as antiemetic drugs. Alkylating drugs were given as a one hour infusion. Thyroid hormone parameters were determined before and on day 1, 2, 3, 4 after drug administration. We observed a significant increase in T4 and fT4 concentrations and a concomitant fall in TSH in either group one day after the administration of alkylating drugs. The effect was most pronounced in group III: T4 increased from 113 +/- 8 nmol/L to 175 +/- 8 (normal: 58-154) and fT4 from 14.0 +/- 0.8 to 24.8 +/- 2.5 pmol/L (normal 10-25). TSH dropped from 1.27 +/- 0.16 to 0.33 +/- 0.07 mU/L (normal 0.3-4). All changes were significant: p < 0.001. Two of the six patients displayed biochemical hyperthyroidism. Also reverse T3 increased significantly. Two days after drug administration a gradual normalization occurred. However, T3, Tg, TBG, Transthyretin and albumin levels did not change throughout the study period. One patient with coexisting hypothyroidism, who received his last thyroxine substitution therapy one day before the administration of cyclophosphamide (as in group I), also demonstrated an increase in T4, fT4 and rT3 and a fall in TSH concentrations. I.v. administrations of cyclophosphamide and ifosfamide induce a transient increase in T4 and fT4 concentrations and a concomitant fall of TSH in the presence of normal Tg, T3 and thyroid binding protein concentrations. These data suggest, that the changes are not due to a release of thyroid hormones from the thyroid itself, but is likewise related to a release of thyroxine from cellular pools such as the liver.

Pregnant Women on Thyroxine Substitution Are Often Dysregulated in Early Pregnancy

Thyroid hormones are important for normal fetal development. Maternal hypothyroidism during early pregnancy is associated with impaired neuropsychological development of children and other adverse outcomes. The primary aim of this prospective study was to determine whether thyroxine-treated pregnant women with hypothyroidism are adequately thyroxine substituted in early pregnancy. A secondary aim was to determine if fetal loss differed between females with thyrotropin (TSH) values within and outside the reference range at their first TSH test, scheduled for 1-2 weeks after verification of pregnancy. This was a prospective open-labeled study. During the years 1997-2002, 119 consecutive pregnancies in 101 females with thyroid diseases were followed at the Department of Endocrinology, Malmö University Hospital. At the first visit, 63 patients, median age 30 years (range 17-45 years), were on thyroxine substitution therapy for hypothyroidism. In these patients 83% were in their first trimester at the time of the initial test. Of the 63 patients on thyroxine substitution for hypothyroidism 32 (51%; Group A) patients had serum TSH values within the reference range at their initial test and 31 (49%; Group B) had serum TSH values outside the reference range. Twelve (19%) had TSH values of <0.40 mIU=L and 19 (30%) had TSH values of >4.0 mIU=l. The fetal loss was 2 of 32 (6%) in Group A compared to 9 of 31 (29%) in Group B ( p < 0.05). In 49% of pregnant women on thyroxine substitution, serum TSH values were outside the reference range when first tested, generally in the first trimester. Fetal loss was significantly greater in pregnant women with abnormal TSH values compared to those with normal TSH values. Thyroid function in pregnant women on thyroxine substitution should be monitored early in pregnancy and carefully followed during pregnancy. The thyroxine dose should be increased as needed early in pregnancy to avoid hypothyroidism.

Transient hypothyroxinaemia in preterm infants

Thyroid hormones are required for normal development of the brain. Transient hypothyroxinaemia is the most common thyroid dysfunction in preterm infants and is defined by temporary low levels of T4, T3 and normal or low TSH. Low T4 levels in preterm infants are associated with persistent neurodevelopmental deficits in cognitive and motor function. Thyroid hormone substitution trials to date are underpowered and show inconsistent results; the question remains — are low T4 levels simply an epiphenomenon? The aetiology of transient hypothyroxinaemia is multifactorial and the components amenable to correction form the basis of the therapeutic strategy: rectification of iodine deficiency in parenteral nutrition; a reduction of non-thyroidal illnesses and attenuation of their severity; and substitution of drugs that interfere with the hypothalamic–pituitary–thyroid axis. Thyroxine substitution therapy should only be done in the context of clinical trials and only in those infants who are hypothyroxinaemic.

Follow-up in 41 multiple endocrine neoplasia type 2 A (MEN 2A) gene carriers after prophylactic thyroidectomy – problems with thyroxine substitution

In children with RET protooncogene mutation curative treatment of medullary thyroid carcinoma (MTC) is possible by prophylactic thyroidectomy. Long term treatment of athyroid children and adolescents carries some problems. We evaluated the long term follow-up of operated gene carriers. In 41 MEN 2A/FMTC gene carriers (28 families) prophylactic thyroidectomy was carried out between the age of 4 to 21 years. 18 families carried mutations in exon 11 codon 634, one in codon 630, 3 families in exon 10 codons 618 or 620 and 6 families in exons 13–15, codons 790,791, 804 or 891. Histology showed no C-cell hyperplasia (CCH) in 2, CCH in 15 patients and MTC in 24 patients (T1 n=21, T2 n=1, T3 n=1, Tx n=1). No patient had lymph node involvement (N0 n=30, Nx n=11). After prophylactic thyroidectomy 35 patients were cured demonstrated by normal basal and pentagastrin stimulated calcitonin levels. In 6 patients either basal or pentagastrin stimulated calcitonin was elevated. In two patients carrying a 634 mutation other endocrinopathies than MTC manifested during follow-up. A 12 year old boy developed pHPT 5 years after thyroidectomy and a 28 year old women had bilateral adrenalectomy 12 years after thyroidectomy. In the follow-up (x=7.6 y, mean 8 y, range 0.2–18.5 y) under thyroxine substitution therapy in many patients TSH was elevated: after one month in 82% (x=54 mU/l, median 44mU/l), after one year in 35% (x=40, median 15 mU/l), even after 5 years 32% of TSH levels were elevated (×=9 mU/l, median 5 mU/l). Therefore sufficient age- and weight-dependent thyroxine dosage has to be substituted directly after thyroidectomy. During follow-up dose adjustment and control intervals of 3 months are necessary in specialized centres. If prophylactic thyroidectomy is done at early ages cure rate is high. Despite this encouraging results thyroxine substitution therapy in the follow-up carries some problems concerning optimal dosage and non-compliance. Therefore TSH has to be estimated in the follow-up every 3 months, especially in children and adolescents.

Left ventricular function in congenital hypothyroidism neonates before and after thyroxine substitution therapy

To evaluate left the systolic and diastolic functions in neonates with congenital hypothyroidism (CH) as well as the effect of thyroxine substitution therapy on left ventricular function and its correlation with thyroid hormones serum levels. M-mode echocardiography was used to examine the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), pulse wave Doppler was used to examine the peak early diastolic mitral inflow velocity (E(m)) and peak late diastolic mitral inflow velocity (A(m)), quantitative tissue velocity imaging (QTVI) was used to examine the systolic peak mitral annular velocity (s(m)), early diastolic peak mitral annular velocity (E(m)), and the late diastolic peak mitral annular velocity (a(m)), and tissue tracking imaging (TTI) was used to detect the systolic mitral annular displacement (MAD) in 40 neonates with congenital hypothyroidism aged 15-28 days before and after 1-month levothyroxine substitution treatment. Thirty normal neonates were used as controls. Chemiluminescent immunoassay was used to measure the TT(3), TT(4) and TSH levels. Correlation analysis was also made between the ventricular function parameters and the serum TT(3), TT(4), and TSH levels. The left systolic function parameters (LVEF, s(m), MAD, E(m) and e(m)) was 0.61 +/- 0.08, 2.60 cm/s +/- 0.60 cm/s, 0.29 cm +/- 0.06 cm, 0.59 m/s +/- 0.12 m/s and 2.72 cm/s +/- 1.43 cm/s respectively, in CH group, and 0.67 +/- 0.06, 3.25 cm/s +/- 0.51 cm/s, 0.41 cm +/- 0.08 cm, 0.72 m/s +/- 0.11 m/s and 4.51 cm/s +/- 1.23 cm/s in control group (P < 0.01). Left function in CH neonates before treatment were all lower than those of the controls (P < 0.01), which significantly increase after 1-months L-T(4) substitution therapy, 0.69 +/- 0.05, 3.46 cm/s +/- 0.64 cm/s, 0.45 cm +/- 0.08 cm, 0.82 m/s +/- 0.17 m/s and 5.09 cm/s +/- 1.37 cm/s, (P < 0.01). Those parameters were positively correlated with TT(4) serum levels (P < 0.01), and were negatively correlated with TSH (all P < 0.01). In particular, MAD, sm, E(m), and em were highly correlated with serum TT(4) and TSH (r = 0.667, 0.538, 0.478, and 0.599 respectively, all P < 0.001;and r = -0.670, -0.521, -0.490, and -0.583 respectively, all P < 0.001). Neonates with CH have lower left systolic and diastolic functions. Early L-T(4) substitution therapy can reverse these changes.

Thyroid Hormone Substitution Therapy Rapidly Enhances Left-Ventricular Diastolic Function in Hypothyroid Patients

Objective: Alterations in thyroid status may lead to changes in both systolic and diastolic function of the heart. Pulsed Doppler echocardiography is a reliable non-invasive means of assessing left-ventricular (LV) diastolic function. The aim of the present study was to evaluate LV diastolic function in patients with primary hypothyroidism receiving thyroxine therapy. Methods: Twelve patients (all females, mean age 47 ± 17, range 16–69 years) with primary hypothyroidism were studied by pulsed Doppler echocardiography. The first examination was made before the start of thyroxine substitution and the second at 37–68 (mean 53 ± 10) days after commencing thyroxine treatment (mean dose 136 ± 22 µg/day). Results: During thyroxine substitution therapy, the hypothyroid patients became clinically euthyroid and serum T4 increased from 51 ± 21 to 119 ± 24 nmol/l; TSH decreased from 50.4 ± 55.3 to 1.2 ± 1.5 mU/l. During therapy, heart rate increased from 61 ± 8 to 68 ± 10 (p = 0.05). The LV posterior wall (7.8 ± 1.0 mm) and interventricular septum thickness (8.0 ± 1.4 mm) were significantly greater in hypothyroid patients than in the control subjects (6.4 ± 1.0 mm, p = 0.007 and 6.8 ± 1.0 mm, p = 0.04, respectively). There was no significant change in LV dimensions and wall thickness during follow-up. E/A_max increased significantly during treatment (from 1.679 ± 0.432 to 1.947 ± 0.335, p = 0.006). The isovolumic relaxation time shortened significantly (from 88 ± 23 ms to 75 ± 24 ms, p = 0.005). Conclusions: The present study shows that LV diastolic function as assessed by pulsed Doppler echocardiography in hypothyroid patients is enhanced by thyroxine therapy during a rather short follow-up period.

Outcome in three siblings with antibody-mediated transient congenital hypothyroidism

A woman receiving thyroxine substitution therapy for acquired hypothyroidism caused by autoimmune thyroiditis gave birth to three babies who had transient primary hypothyroidism. All three babies had elevated thyrotropin levels on neonatal screening, but one had normal thyroxine values. Thyrotropin receptor–blocking antibodies were present in maternal serum and in the three neonates. Each baby also had a different congenital malformation. The neurodevelopmental outcome of the children appeared related in part to maternal thyroxine levels, which suggests that transplacental transfer of thyroxine may protect the fetal brain. (J P EDIATR 1995;127:275-7)

Effect of thyroid function on concentrations of lipoprotein(a)

The effect of thyroid hormones on concentrations of lipoprotein(a) [Lp(a)] was analyzed in 60 patients with active thyroid dysfunction (hyperthyroidism 30 cases, hypothyroidism 32 cases, and 2 cases with opposite changes) and after normalization of the thyroid state. Treatment of hyperthyroidism increased the mean Lp(a) concentrations by 60% (from 73 to 102 mg/L, P < 0.002); at the same time, low-density lipoprotein cholesterol (LDL-C) increased by 53% (from 2.6 to 3.7 mmol/L, P < 0.0001) and apolipoprotein B (apo B) by 35% (from 0.91 to 1.17 g/L, P < 0.0005). In hypothyroidism, the opposite changes were observed: mean Lp(a) decreased from 136 to 114 mg/L (10%, P < 0.02), LDL-C from 4.6 to 3.9 mmol/L (13%, P < 0.01), and apo B from 1.51 to 1.20 g/L (14%, P < 0.01). Although the changes in Lp(a) concentrations did correlate with changes of LDL-C during treatment of hyperthyroidism (r = 0.43, P < 0.05), and with changes in apo B during thyroxine-substitution therapy for hypothyroidism (r = 0.46, P < 0.05), we observed no associations between Lp(a) and LDL-C or apo B in the euthyroid state. These data cannot rule out the possibility that the thyroid hormone-induced increase in LDL-C receptor activity was responsible for the decreased concentrations of Lp(a) in hyperthyroidism. Given that LDL-C is approximately 30% of the Lp(a) molecule but the changes in Lp(a) concentrations are comparable with those in LDL-C (60% vs 53%), and given that Lp(a) is metabolized by an LDL-C-receptor-independent pathway, the present data suggest a direct effect of thyroid hormones on Lp(a) synthesis.

Reproductive Endocrine Functions in Men with Primary Hypothyroidism: Effect of Thyroxine Replacement

Reproductive endocrine functions were studied in men with primary hypothyroidism during the hypothyroid phase and after achieving euthyroid status with thyroxine substitution therapy. Hypergonadotropism [luteinising hormone (LH), 18.7 +/- 7.3 IU/l; follicle-stimulating hormone (FSH), 6.3 +/- 2.0 IU/l], low serum testosterone (6.1 +/- 2.8 nmol/l), low serum sex-hormone-binding globulin (SHBG; 13.2 +/- 2.0 nmol/l) and subnormal testosterone response to human chorionic gonadotropin hCG; (30% increase in serum testosterone following hCG) observed during the hypothyroid phase were restored to normal (LH, 7.2 +/- 2.0 IU/l; FSH, 2.7 +/- 0.9 IU/l; testosterone, 12.9 +/- 2.7 nmol/l; SHBG, 26.5 +/- 8.4 nmol/l, and 2-fold increase in serum testosterone following hCG) with thyroxine substitution therapy. Some improvement in sperm count and motility was also observed.

Thyroid function in patients with pustulosis palmoplantaris

Fifty consecutive patients (45 women and 5 men) with pustulosis palmoplantaris were evaluated for thyroid disease. Five women had previously had thyroid disorders for which they were receiving thyroxine substitution therapy. Of the other 40 women three had a raised serum concentration of thyroid-stimulating hormone and nine had high concentrations of antibodies against thyroid “microsomal antigen.”. During a 4-year follow-up hypothyroidism developed in two women with initially raised thyroid-stimulating hormone, and laboratory test results for one woman indicated subclinical hyperthyroidism. Four of nine patients with thyroid abnormality also had evidence of gastric autoimmunity. Of the patients 94% smoked at the onset of pustulosis palmoplantaris compared with 33% in age-and sex-matched healthy controls. The prevalence of thyroid disease in women with pustulosis palmoplantaris was significantly higher than in a comparable population sample of women from the same geographic region. We conclude that patients with pustulosis palmoplantaris should be screened for thyroid disease.

Pyramidal cortical cell morphology studied by multivariate analysis: effects of neonatal thyroidectomy, ageing and thyroxine-substitution therapy

The changes produced on the whole dendritic morphology of layer III cortical pyramidal neurons by neonatal hypothyroidism, induced in rats by thyroidectomy at 10 days of age (T), as well as those changes related to ageing, have been studied in rats at 40 and 80 days of age. For these purposes, the dendritic structure of these neurons was defined by a set of 10 variables whose measurements were analyzed using multivariate methods. The effect of tyroxine (T 4) substitution therapies applied to T rats between 12–40 and 30–80 days of age has been further investigated with the same mathematical methodology. The results obtained from the analyses performed show that hypothyroidism affects both the apical tuft and the basal dendritic arborization of these neurons. The observed damage was similar: a decrease of the total length of the dendritic segments of the apical tuft and the basal arborization. This change, however, was detected in these two different subregions with a different timing. These results seem to reinforce our findings concerning the selective effect of T on different sites of these neurons. On the other hand, 3 morphological changes have been revealed regarding the development of the pyramidal neuron studied: (1) the total length of the apical tuft dendritic segments increases from 40 to 80 days of age; (2) the total length of the basal dendritic segments decreases from 40 to 80 days of age; and (3) the perimeter of the cell body decreases from 40 to 80 days of age. Finally, the results obtained did not allow us to detect any recovery of the damage induced by T, as a consequence of the T 4 substitution therapies applied.

Influence of thyroid substitution therapy and thyroid autoantibodies on the value of serum thyroglobulin in recurring thyroid cancer

The study was performed to evaluate the influence of thyroxine substitution therapy and the presence of thyroglobulin antibodies (TgAb) on the usefulness of serum thyroglobulin (Tg) measurements in the follow-up of patients treated for well differentiated thyroid carcinoma. Seventy-two consecutive patients with differentiated thyroid cancer and eight with medullary carcinoma as well as controls were studied on one or more occasions and blood was drawn for measurement of serum Tg, TgAb, TSH and thyroid hormones. In 23 patients the hormonal substitution was withdrawn and 3-4 weeks later new blood samples and a 131I scintigraphy was performed. Eighteen patients were shown to have recurrence or metastases. Four of these had TgAb, two had normal Tg values, and the remaining 12 had extremely elevated levels. Those with TgAb and normal Tg values all had high Tg levels off thyroxine substitution. The 54 patients without evidence of recurrence had low levels of serum Tg except for one with highly elevated values. Based on the results from this and other studies is concluded that serum Tg is an important adjunct in the follow-up of patients with well differentiated thyroid carcinoma, but certain limiting factors have to be taken into account, i.e., the radicality of surgery, the sufficiency of the substitution, the presence of TgAb and the method for measurement of Tg.

Computerized CFF: Reliability and Validity of Two Psychophysical Techniques

Two computerized CFF measures have been implemented in our laboratory and used in several studies. One method is based on the traditional "method of limits" threshold determination technique (CFF-ML). Process-controlled optimization of individual stimulus parameters (starting points and center frequency of ascending and descending sweeps) were shown to give a significant increase in test-retest reliability as compared with a non-computerized version. In subsequent studies, test-retest reliabilities (> 24 h) for CFF-ML have regularly exceeded .90. Criticism against the method of limits for not separating sensory and response factors was the basis for the design of a forced choice, three-alternative, process-controlled CFF method (CFF-3). The reliability of CFF-3 appears to be high (.90-.95), there are virtually no order effects (even after 20 retest sessions of four minutes each), and the "exposure time" for a reliable threshold determination can be made short enough to study fast drug onset effects, for instance after smoking. Both CFF methods appear to have a satisfactory validity, allowing demonstration of significant effects in small samples of subjects, of e.g. variations in cerebral blood flow, effects of thyroxine substitution therapy in hypothyroid patients, and effects of sedative and CNS stimulant drugs.

Cerebral function in hypothyroid patients. A study of the vigilance level in patients with hypothyroidism before and during substitution therapy.

Mental performance was studied in 6 hypothyrotic patients before, seven weeks after and one year after initiation of thyroxine substitution therapy. Performance as measured by critical flicker-fusion (CFF) and vernier visual acuity (KVAT) improved significantly after 7 weeks of substitution therapy, and improved still further, although not significantly, after 1 year. Performance as measured by two reaction time tasks was not significantly improved, either after 7 weeks or after 1 year. The results were interpreted in terms of the complexity of the measures used, more complex measures being more affected by the disease through summing of several ‘unit impairments’. Further, 3 subjects were studied in detail with repeated measurements of CFF. 1 subject was studied with T4 substitution, another with T3 substitution and 1 subject with T4 substitution and T4 substitution plus T4 propylthiouracil blocking of T4 to T3 metabolism. With T4 substitution there was a distinct increase in performance, with a delay of 2-3 weeks after a dose change. With T3 substitution in a dose corresponding to T4 to T3 metabolism there was no change in performance.

Serum a1-fetoprotein levels in congenital hypothyroidism

Serum a1-fetoprotein (A.F.P.) was measured by double antibody radioimmunoassay in 4 boys and 5 girls with congenital hypothyroidism aged 1 to 3 months and in 20 normal infants matched for age and sex. Thirty days following the initiation of thyroxine substitution therapy wich was instituted upon diagnosis (A.F.P.) was remeasured. Serum A.F.P. in the hypothyroid infants was found to be raised before therapy (147.6±20.7 ng/ml) compared to normal infants(28±7.26 ng/ml). This difference was highly significant (p < 0.001). After one month therapy with thyroxin there was a significant fall in A.F.P. levels(51+19.7 ng/ml). It is suggested that if elevated AFP levels are found during A.F.P. screening programmes hypothyroidism should be excluded.