南京地区1998-2009年新生儿先天性甲状腺功能减低症筛查及治疗随访结果分析

目的 总结并分析1998年1月- 2009年12月南京地区新生儿先天性甲状腺功能减低症(CH)的筛查结果.方法 采集出生72 h新生儿442 454例的足跟血滴于滤纸上,采用时间分辨免疫法测定滤纸血斑促甲状腺激素(TSH),阳性者召回进一步测定静脉血TSH、三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、游离T3(FT3)、游离T4(FT4)以明确诊断.确诊者立即开始予左旋甲状腺素片(4.3～12.0μg·kg-1·d-1)替代治疗,定期监测其甲状腺功能,测量其身高、体质量,其中68例患儿子智力测试,以评估疗效.结果 12 a共筛查442 454人,确诊CH 183例,发病率为0.41‰,对117例进行随访.初始治疗时间的中位数为18 d(7～67d),初始左旋甲状腺素的平均剂量为7.35 μg·kg-1·d-1.CH患儿的身高、体质量结果基本达到正常参照标准.盖泽尔婴幼儿发展量表(GESELL)测试结果显示1例智能发育落后,8例智能发育迟缓.T4、FT4的治疗前水平与患儿的GESELL测试总分、适应性及精细运动均呈正相关(Pa＜0.05).结论 经筛查确诊的CH患儿,应尽可能早地进行激素替代治疗,可有效改善其预后.因此新生儿筛查及随访治疗工作值得推广和完善.     

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement

OBJECTIVE—To determine the feasibility of annual hypothyroid screening of children with Down''s syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children.DESIGN—Establishment of a register of school children with Down''s syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre.SUBJECTS—All school age children with Down''s syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8.RESULTS—200 of 214 school children with Down''s syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto''s thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is ? 8.9%.CONCLUSION—Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down''s syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Long‐term stability of thyroid hormones and DNA in blood spots kept under varying storage conditions

Background: Congenital hypothyroidism is screened using blood spotted on filter paper that may be transported from remote areas to central testing facilities. However, storage conditions and transportation may affect sample quality. Methods: We examined long‐term stability of thyroid‐stimulating hormone (TSH) and thyroxin (TT4) in blood spotted on filter paper, which was stored at room temperature (RT), 4°C and ?20°C under continuous or intermittent power supply (six hours on and six hours off around the clock.) Hormone levels in the discs were measured periodically for up to ten years. Extraction of DNA from blood spots and polymerase chain reaction were performed. Results: Our results showed that TT4 was stable for up to 6.1, 5.34 and 5.16 years when stored at ?20°C, 4°C and RT, respectively. TSH was stable for up to 2.7 years at RT, and for up to 6.5 and 4.1 years when stored at ?20°C and 4°C, respectively, under continuous power supply. However, under intermittent power supply, TSH was stable for up to 3.8 and 2.5 years when stored at 4°C and ?20°C, respectively. Mitochondrial cytochrome oxidase and sex‐determining region of Y chromosome genes were successfully amplified from DNA extracted from the blood spots. Conclusion: Our data indicate that TT4 and TSH are most stable in blood spots stored at ?20°C under continuous power supply. However, they can be stored at RT or at 4°C and ?20°C under interrupted power supply for at least 2.5 years. Moreover, the DNA extracted from the blood spots was intact and suitable for genetic studies.     

School based screening for hypothyroidism in Down's syndrome by dried blood spot TSH measurement.

OBJECTIVE: To determine the feasibility of annual hypothyroid screening of children with Down's syndrome by measuring thyroid stimulating hormone (TSH) on dried blood spots at school, and to describe the outcome in positive children. DESIGN: Establishment of a register of school children with Down's syndrome, and procedures for obtaining permission from parents, annual capillary blood samples, TSH measurement, and clinical assessment of children with TSH values > 10 mU/litre. SUBJECTS: All school age children with Down's syndrome within Lanarkshire and Glasgow Health Boards during 1996-7 and 1997-8. RESULTS: 200 of 214 school children with Down's syndrome were screened. Four of the unscreened children were receiving thyroxine treatment, and only 5 remained unscreened by default. 15 of the 200 children had capillary TSH > 10 mU/litre, and all but 1 had evidence of Hashimoto's thyroiditis. Seven of the 15 children started thyroxine treatment immediately, 6 with a pronounced rise in venous TSH and subnormal free thyroxine (fT4), and one with mildly raised TSH and normal fT4 but symptoms suggesting hypothyroidism. Eight children with mildly raised venous TSH and normal fT4 were left untreated; 1 year after testing positive, fT4 remained > 9 pmol/litre in all cases, but 4 children were started on thyroxine because of a rise in TSH. TSH fell in 3 of the 4 remaining children and there was a marginal rise in 1; all remain untreated. The prevalence of thyroid disease in this population is >/= 8.9%. CONCLUSION: Dried blood spot TSH measurement is effective for detecting hypothyroidism in Down's syndrome and capillary sampling is easily performed at school. The existing programme could be extended to the whole of Scotland within a few years.     

Results of a regional cord blood screening programme for detecting neonatal hypothyroidism.

Our regional cord blood screening programme for detecting neonatal hypothyroidism using initial cord blood thyroxine (T4) determinations, with supplemental thyrotropin (TSH), and triiodothyronine resin uptake (T3U) measurements, gave an incidence of thyroid abnormalities of 1/3000 births, with 1/5000 infants having severe primary hypothyroidism. No hypothyroid infant detected in the programme had been suspected clinically before the screening and, in retrospect, only a few babies had any signs of hypothyroidism. Supplemental TSH and T3U determinations were required on 8-12% of the population screened initially with a T4 test to avoid missing affected cases. With an initial T4 and supplementary TSH and T3U testing on cord blood serum, recalls to exclude primary hypothyroidism were reduced to 0.16% of the screened population. The incidence of abnormalities detected in this cord blood screening programme was comparable with that reported by others using neonatal dried blood screening methods, indicating that cord blood screening can be effective provided the appropriate recall criteria and transport conditions are used. Nevertheless, for several practical reasons, neonatal dried blood methods are recommended as the screening test of choice for surveying large populations over extensive geographical areas.     

SCREENING FOR CONGENITAL HYPOTHYROIDISM

ABSTRACT. Larsson, A., Ljunggren, J. G., Ekman, K., Nilsson, A. and Olin, P. (Departments of Paediatrics and Child Psychiatry, Karolinska Institute, St. Goran's Children's Hospital; the Department of Medicine, St. Göran's Hospital; and the PKU Section of the Department of Bacteriology, National Bacteriological Laboratory, Stockholm, Sweden). Screening for congenital hypothyroidism. I. Laboratory results of a pilot study based on dried blood samples collected for PKU screening. Acta Paediatr Scand, 70:141, 1981. – A pilot study was performed to establish optimal conditions for nation-wide screening for congenital hypothyroidism in Sweden. The levels of T₄ and TSH were determined by automated radioimmunoassay in the dried blood spots, routinely collected for PKU screening on the fifth postnatal day, from all 1979, 2 infants born in the Stockholm area during a 14-month period. To identify safe minimum recall criteria for routine use, infants were recalled if the TSH level was more than 30 mU/l of plasma or–if they were not preterm–the T₄ concentration was less than -2 S.D. of the mean. Altogether 160 infants were recalled. Seven newborns with congenital hypothyroidism were identified, 6 with primary and one with secondary hypothyroidism. Five infants had decreased levels of thyroxine-binding globulin. The results of the follow-up analyses from recalled infants showed that determination of the reverse-T₃ level may be of diagnostic value around the 23rd day of life. The results of the clinical investigation of recalled infants are reported in a subsequent paper and a programme for nation-wide screening for congenital hypothyroidism is proposed.     

Neonatal screening for hypothyroidism in Greece

One year's experience in screening for congenital hypothyroidism in Greece is reported. Thyroidstimulating hormone (TSH) determination by a radioimmunoassay on dried blood spots was selected as the screening method. During the first year of screening 75,879 newborn infants were tested from Guthrie blood spots taken on the 5th day of life. Eighteen cases of primary congenital hypothyroidism with serum TSH levels over 100 IU/ml were detected, giving an incidence of 1:4200. One case had already been diagnosed clinically. Replacement treatment was started between the 22nd and the 50th days of life.     

Iodine status of pregnant women living in urban Johannesburg,South Africa

Adequate intake of iodine is important during pregnancy because of its essential role in foetal growth and neurodevelopment. Data on iodine status of South African pregnant women are scarce, and the salt reduction policy implemented in 2016 may decrease iodine intake of South Africans. This cross-sectional study assessed the iodine status of pregnant women residing in urban Johannesburg, South Africa. A total of 250 pregnant women were enrolled into the ‘Nutrition during Pregnancy and Early Development’ (NuPED) study and 312 pregnant women into the ‘Assessment of dried blood spot thyroglobulin in pregnant women to redefine the range of median urinary iodine concentration that indicates adequate iodine intake, South Africa’ (STRIPE-SA) study and were included in this analysis. Urinary iodine concentration (UIC) was analysed in a spot urine sample. Thyroglobulin (Tg) was measured in serum, and thyroid-stimulating hormone (TSH) and total thyroxine (tT4) were measured in dried blood spots. The median [interquartile range (IQR)] UIC of pregnant women was 144 (84–234) μg/L. Women in the first (n = 99), second (n = 262) and third (n = 174) trimester had a median UIC of 133 (81–316), 145 (84–236) and 156 (89–245) μg/L, respectively (p = 0.419). Median TSH, tT4 and Tg were 2.7 (2.3–3.2) mU/L, 202 (163–236) nmol/L and 9.2 (5.4–17.9) μg/L, respectively. Based on the median UIC, pregnant women residing in urban Johannesburg may be borderline iodine deficient. These findings highlight the need for ongoing monitoring of iodine status among vulnerable pregnant women, especially considering the recently introduced salt reduction policy in South Africa.     

Finnish national screening for hypothyroidism

National cord blood screening for congenital hypothyroidism has operated in Finland with complete coverage since 1980. A low frequency of false positives, 0.08%, was achieved by supplementing the TSH screen with a T4 determination in borderline samples. Among 175188 infants the incidence of (unconfirmed) hypothyroidism was 1/2637. The median age at start of therapy was 6 days. The programme imposed a 2–3 week therapy on the false positive cases. This did not appear to cause any adverse effects. A mechanism for masking congenital hypothyroidism was observed: two athyroid infants were euthyroid at birth because of feto-fetal transfusion.Abbreviation T4 serum total thyroxine     

Raised serum TSH in hypothyroidism.

It is desirable to detect early hypothyroidism of the mildest degree even before conventional tests of thyroid function become abnormal. Serum TSH levels (normal: undetectable to 4 muU/ml) rise in patients with mild hypothyroidism long before serum T4 and T3 levels fall. In the patient described the serum TSH level was 310 muU/ml, while other tests of thyroid function gave normal results. After treatment with thyroxine, serum TSH returned to normal. It should now be accepted that patients with mild hypothyroidism have a raised serum TSH and that thyroid insufficiency can be confidently excluded if the serum TSH concentration is normal. It is thus important to assay serum TSH when suspicion of hypothyroidism is aroused.     

Thyroxine (T4) immunoassay using a filter paper blood samples for screening of neonates for hypothyroidism.

A rapid, sensitive radioimmunoassay for thyroxine (T4) is described which requires a specimen of dried blood on filter paper. One milliliter of glycine-acetate buffer containing anti-T4 antibody, tracer T4, and sodium salicylate is added to a tube containing a 1/8-inch dot of the filter paper specimen. After incubation overnight, bound and free hormone are separated by addition of dextran-coated charcoal. Quantitation is obtained using a standard curve prepared from dots of dried blood samples with known T4 content. The dot remains in the solution throughout the procedure. Recovery of T4 is 95% and intra- and interassay coefficients of variation are both less than 10%. The mean T4 content of 983 samples from the 3-day-old infants was 189 +/- 48 pg T4/dot (mean SD). This corresponds to the T4 in 1.5 mul plasma, and thus the estimated plasma T4 in these infants is 12.6 +/- 3.2 mug T4/100 ml. Nine neonates had repeated samples in which the T4 content was lower than 2 SD below the mean. All of these infants had normal cord thyroid-stimulating hormone (TSH) concentrations and thus presumably do not have primary hypothyroidism. The method should be useful for screening neonates (and older infants), since it can be adapted for use with the punch-index machine for automated processing, no prior extraction of T4 from the dot is required before quantitation, and the small size of the sample allows repeated tests of suspicious results.     

Congenital hypothyroidism: Clinical and laboratory characteristics in infants detected by neonatal screening

The clinical and laboratory characteristics of infants with neonatal hypothyroidism, and the age at which treatment was started are reviewed. The incidence of primary hypothyroidism was 1 in 3488 live births. Most of these cases were detected in a cord blood screening programme which was carried out between October 1973 and May 1980 in the Toronto region. Forty-eight infants with primary persistent hypothyroidism were classified by technetium scintiscanning as follows: 12 with athyrosis (non-visualised thyroid glands), 14 with ectopic thyroid glands, and 14 with goitrous thyroid glands. The remaining 8 infants comprised 4 with hypoplasia and 4 with transient hypothyroidism (2 idiopathic and 2 iodide induced). Although infants with athyrosis had a lower mean thyroxine value, their values overall were not significantly different from those of the other groups. Some infants, particularly those who were goitrous or ectopic, initially had normal thyroxine values. Skeletal maturation was more often delayed in athyrotic infants than in the ectopic or goitrous group. Radioactive iodine uptakes were appreciably higher in the goitrous group, and there was no significant difference between athyrotic and ectopic groups. The mean age at which treatment was started for all patients was 25 (range 6-120) days. The average age for starting treatment using initial thyroxine and secondary thyrotrophin testing in the initial stages of the cord blood screening was 36 days. The use of initial cord serum or dried blood thyrotrophin reduced the start of treatment to 14 days. It is concluded that: (1) It is important to determine the precise anatomical diagnosis, the biochemical severity, and the age at which treatment is started in order to assess the benefits of regional screening programmes in the detection of neonatal hypothyroidism. (2) Routine technetium scintiscanning before the start of treatment helps to determine the diagnosis. (3) Radioactive ¹³¹-I thyroid uptake studies are no longer routinely recommended; this is because of the radiation hazard and the lack of specificity in differentiating between the various anatomical types. (4) The feasibility of cord blood screening to detect the various causes of neonatal hypothyroidism is confirmed. (5) The time between final diagnosis and the institution of treatment can be reduced by 2 or 3 weeks if a thyrotrophin test is used initially from cord blood serum or, preferably, from dried blood spotted on filter paper; the latter is easier to post to a screening laboratory.     

Severe rhabdomyolysis and acute renal failure in an adolescent with hypothyroidism

Hypothyroidism has been reported rarely as the cause of rhabdomyolysis in adults and children. We present here a non-compliant adolescent with a diagnosis of hypothyroidism who developed rhabdomyolysis and acute renal failure with no additional predisposing factor. A 13-year-old girl with a previous history of hypothyroidism due to thyroid hypoplasia presented with generalized myalgia, malaise, vomiting, and oliguria lasting for three days. Neurological examination revealed bilateral marked weakness and tenderness of muscles of both lower and upper extremities. Urine had bloody appearance and urine analysis showed blood reaction with dipstick test, but there were no erythrocytes on microscopic examination. Serum creatine phosphokinase and myoglobin levels were elevated. Thyroid stimulating hormone (TSH) levels were high, and free thyroxine (T4) and triiodothyronine (T3) levels were low, compatible with uncontrolled hypothyroidism. Renal function tests showed acute renal failure. Other causes of rhabdomyolysis such as muscular trauma, drugs, toxins, infections, vigorous exercise, and electrolyte abnormalities were excluded. Hemodialysis was administered for 24 sessions. After L-thyroxine therapy, thyroid function tests normalized, muscle strength improved, serum muscle enzyme levels returned to normal levels, and renal function tests recovered. One must be aware that rhabdomyolysis may develop in a non-compliant patient with hypothyroidism.     

Direct assay of free thyroxine in children. Application to the monitoring of the treatment of hypothyroidism

A direct measurement of free thyroxine (FT4) by a radio-immunologic method using an analogue of thyroxine as tracer allowed to establish the normal values in 341 children from birth to puberty. These values were used as reference for the determination of free T4 in the diagnosis and management of treatment for congenital hypothyroidism. In 44 treated hypothyroid children, there was a positive correlation between the serum concentration of free T4 and the amount of levothyroxine given daily (r = 0.46, p less than 0.01). There was also a negative correlation between free T4 and serum TSH (r = 0.59, p less than 0.001). Thus, the measurement of free thyroxine seems to be a more reliable, more accurate and more sensitive parameter than that of total thyroxine or TSH for controlling the treatment of congenital hypothyroidism.     

Central Congenital Hypothyroidism Detected by Neonatal Screening in Sapporo, Japan (2000–2004): It’s Prevalence and Clinical Characteristics

In Sapporo, Japan, a neonatal screening program for congenital hypothyroidism (CH) has employed measurement of free thyroxine (T4) and TSH in the same filter-paper blood spot. This system has enabled us to identify primary CH and central CH during the neonatal period. The aim of this study was to clarify the prevalence and clinical characteristics of central CH. For this purpose, the screening program requested serum from infants with free T4 concentrations below the cut off value regardless of the TSH levels. Between January 2000 and December 2004, 83,232 newborns were screened and six central CH patients were detected as a result of follow-up of low free T4 and non-elevated TSH screening (1:13,872). This frequency is higher than in other studies. Four patients showed multiple pituitary hormone deficiency with pituitary malformations on magnetic resonance imaging. One patient was diagnosed as having Prader-Willie syndrome. The remaining patient was considered to have isolated central CH. Our study demonstrated that the frequency of central CH is 1:13,872. Free T4 measurement would also be advantageous in early recognition of multiple pituitary hormone deficiency.     

Screening for hypercholesterolaemia in 10,000 neonates in a multi-ethnic population

An immunoassay was developed for the detection of hypercholesterolaemia in dried blood spots collected from 6-day-old neonates. Blood spot samples (9,673) were subjected to immunoturbidimetric assay to determine the levels of apolipoprotein B (apoB), an index of plasma low density lipoprotein, and of apolipoprotein A-1 (apoA-1), an index of plasma high density lipoprotein. Infants with raised apoB or a reduced apoA-1/apoB ratio were recalled, retested and, if appropriate, referred to the Vascular Risk Clinic at King's College Hospital for medical management. A total of 189 were recalled for further testing; of whom 82 (45%) attended the recall clinic. A group of 16 families (24 individuals) had abnormal lipid profiles; of these, 7 families (14 individuals) had lipid profiles consistent with inherited hypercholesterolaemia. Conclusion Neonatal screening for hypercholesterolaemia using blood spot apolipo- protein measurements is feasible but ethnic variations in disease prevalence must be considered in the design of a screening programme. Received: 2 September 1997 / Accepted in revised form: 22 February 1999     

Cord blood thyroxine and thyroid stimulating hormone screening for congenital hypothyroidism: how useful are they?

AIM: To determine and compare the usefulness of cord blood screening for free thyroxine (FT4) and thyroid stimulating hormone (TSH). BACKGROUND: There is a vast amount of literature on capillary heel prick screening tests, but relatively little on cord blood testing particularly FT4. For a decade all infants born at Tawam Hospital had cord blood FT4 and at Oasis Hospital cord TSH measured through the hospital-based screening programme. On January 1st 1998, the national screening programme (NSP) for congenital hypothyroidism (CH) in the United Arab Emirates (UAE) started using capillary TSH measurement (Delfia method). Since then newborns in both hospitals have been screened both ways, i.e. cord blood and capillary blood screening. METHODS: We reviewed retrospectively all infants born from January 1998 until the end of June 2004 with CH who had double screening: cord FT4 or TSH and 4th-5th day TSH screening. RESULTS: Thirteen infants (one in 1,778) had CH in Tawam Hospital. In six of these the cord blood FT4 was low (<9.1 pm/l) (0.73 ng/dl) and in seven the cord blood FT4 was normal, i.e., over half were missed. Eight infants (one in 1,198) had CH in the Oasis Hospital. Cord blood TSH was high in six of them (>13 IU/l) and two were normal. Cord FT4 detected the most severe cases, but missed most others. Cord TSH detected six out of eight cases, but there was a recall rate of one in 23. CONCLUSIONS AND RECOMMENDATIONS: Cord FT4 identifies only infants with severe CH. Cord TSH is more sensitive than cord FT4 screening. Capillary TSH dried blood spot testing on the 3rd-5th day is the most sensitive method.     

Development of Bile Acid Metabolism in Neonates during Perinatal Period | Part 2. Mass screening of congenital biliary atresia by radioimmunoassay using dried blood spot

Inour country, congenital biliary atresia (CBA) has occurred in approximately 1 of 10,000 live births, but its prognosis has been extremely poor. In the mass screening of this disease, glycocholic acid (GCA) or chenodeoxycholic acid (CDCA) level in dried blood spots on filter paper in5-day-old neonates was determined by radioimmunoassay (RIA).
To determine GCA in dried blood spots on filter paper, the procedures in this experiment were modified using commercial kit for serum.
The mean GCA level of controls (n=391) was 5.88±4.28 nM/ml and that of CBA (n=22) was 14.1 ±3.1 nM/ml. On the other hand the mean CDCA level of controls (n=86) was 5.86 ±3.07 pM/l disc that of CBA (n=22) was 30.0 ±35.9 pM/l disc. When the criterion is assumed to be more than 16 nM/ml of GCA level or 10 pM/l disc of CDCA level, false negative diagnoses of CBA are 31.8% and 18.2% respectively. On the other hand false positive diagnoses of CBA are 6.9% and 3.5% respectively. It was thought that false negative diagnosis on mass screening with GCA level would decrease using fresh dried blood spot within 2 weeks after taking blood.
In 22 CBA cases, the GCA levels in dried blood spots on filter paper were not always parallel with the CDCA levels.     

A Screening Method for Adrenoleukodystrophy Using a Dried Blood Spot on Filter Paper

The authors have devised a new, simple method for the diagnosis of adrenoleukodystrophy (ALD) using a dried blood spot sample. Fatty acid from the dried blood spot was extracted and methylated with HCl-methanol. Fatty acid methyl esters were analyzed by gas chromatography-mass spectrometry. Fatty acid composition of the blood spot from five patients with ALD and from five healthy controls was determined from the mass chromatogram of the m/z 143 ion, [(CH₂) ₆ COOCH₃]±. The ratios of tetracosanoic acid to docosanoic acid (C24:0/C22:0) and of hexacosanoic acid to docosanoic acid (C26:0/C22:0) were significantly greater in ALD patients than in controls. The C24:0/C22:0 ratios of ALD patients and of controls were 2.08 ± 0.33 and 1.47 ± 0.16 (mean ± SD), respectively. The C26:0/C22:0 ratios of ALD patients and of controls were 0.31 ± 0.024 and 0.092 ± 0.041, respectively. The fatty acid composition of the dried blood spot did not change at room temperature within a week. Since the specimens can be sent by mail, this method could be applied to the screening of other “peroxisomal” diseases, such as neonatal ALD and Zellweger syndrome, as well.     

Value of the ultrasensitive assay of plasma TSH for the surveillance of replacement treatment in children with congenital hypothyroidism

This study proposes some improvements in monitoring congenital hypothyroidism (CH) using an ultrasensitive plasma TSH assay (usTSH). Patients were 42 CH treated with levo-thyroxine (L-T4) for at least 6 months. Controls were 25 age-matched children (C). Comparative determinations of plasma TSH with classical radioimmunoassay (RIA), on one hand, and usTSH on the other hand, revealed RIA values to be beneath the sensitivity threshold in 3 C and in 15 CH. With usTSH, all the TSH values were assayed over the sensitivity threshold. Therefore the CH could be placed into 3 subgroups according to whether their values were below (n = 17), equal to (n = 15) or above (n = 10) those determined for C. Mean plasma levels of thyroxine (T4) or free thyroxine (FT4) were higher in the CH group, considered as a whole, than in C (p less than .01). Furthermore these values did not appear to be correlated with those in the TSH subgroups, anymore than they were with those of therapeutic doses of L-T4 administered. These discrepancies may be explained in terms of metabolism of exogenous thyroid hormones. UsTSH plasma values would therefore reflect the action of thyroid hormones on thyreotropic cells. To this extent the assay constitutes a sensitive index in detecting both therapeutic insufficiencies and overtreatments.