Screening of geriatric patients for thyroid dysfunction with thyrotropin-releasing-hormone test, sensitive thyrotropin and free thyroxine estimation

Hospitalized geriatric patients (N = 354) from an iodine-deficient area were screened with sensitive thyrotropin (TSH), free and total thyroxine (FT4, T4) and total triiodothyronine (T3) to determine the occurrence rate of clinical and subclinical thyroid dysfunction. The diagnostic value of the tests was compared to each other and to that of the thyrotropin-releasing-hormone test (TRH-test) in order to find the optimal first line screening test in geriatric patients. Clinical hyperthyroidism was found in 13, subclinical hyperthyroidism in 10, overt hypothyroidism in 6 and subclinical hypothyroidism in 8 cases. 20.6% of the patients were euthyroid but had subnormal TSH response to TRH, as a sign of possible thyroid autonomy. The low occurrence rate of clinical thyroid disorders (4.8%) does not justify the screening of geriatric patients in general, but the high probability of thyroid autonomy makes reasonable the investigation of every geriatric patient before iodine administration. Suppressed basal TSH and high FT4 were found to be both sensitive and specific in diagnosing clinical hyperthyroidism, but the predictive value was insufficient; elevated T4 and T3 are specific, but not sensitive. Basal TSH is sensitive, specific and has a good predictive value in diagnosing euthyroidism, whereas normal T4, FT4 or T3 are not specific enough for euthyroidism. Basal TSH is better as a first line test of thyroid function than FT4. A normal basal TSH confirms euthyroidism by itself. Other tests (TRH test, T4, FT4, T3) are necessary to elucidate the clinical importance of a subnormal or suppressed basal TSH.     

Relationship of iodide-induced increase in TSH response to TRH to changes in serum thyroid hormones.

Large doses of iodide (500 mg three times a day) administered to normal men for 10--12 days caused a rise in basal serum TSH and a concomitant rise in the peak TSH response to TRH. The basal and peak levels of TSH were highly correlated (p less than 0.001). However, the iodide-induced rise in the peak TSH after TRH was poorly correlated with concomitant changes in serum thyroid hormones. Serum T3 wa not lower after iodide and, while serum T4 was somewhat lower, the fall in serum T4 was unexpectedly inversely rather than directly correlated with the rise in the peak TSH response to TRH. Thus, increased TSH secretion after iodide need not always be directly correlated with decreased concentrations of circulating thyroid hormones even when large doses of iodide are used. Clinically, a patient taking iodide may have an increased TSH response in a TRH stimulation test even though there is little or no change in the serum level of T3 or T4.     

Effect of triiodothyronine administration on the plasma TSH and prolactin responses to TRH in patients with hypothalamic-pituitary insufficiency.

A study was carried out in 10 patients with multiple pituitary hormone deficiencies to determine the response of thyroid-stimulating hormone (TSH) and prolactin (PRL) to thyrotropin-releasing hormone (TRH) and their suppressibility by treatment with triiodothyronine (T3) given at a dose of 60 microgram/day for 1 week. In 3 patients the basal tsh values were normal and in 7 patients, 2 of whom had not received regular thyroid replacement therapy, they were elevated. The response of TSH to TRH was normal in 6 patients and exaggerated in 4 (of these, 1 patient had not received previous substitution therapy and 2 had received only irregular treatment). The basal and stimulated levels of TSH were markedly suppressed by the treatment with T3. The basal PRL levels were normal in 7 and slightly elevated in 3 patients. The response of PRL to TRH stimulation was exaggerated in 2, normal in 6 and absent in 2 patients. The basal PRL levels were not suppressible by T3 treatment but in 4 patients this treatment reduced the PRL response to TRH stimulation. From these findings the following conclusions are drawn: (1) T3 suppresses TSH at the pituitary level, and (2) the hyperreactivity of TSH to TRH and the low set point of suppressibility are probably due to a lack of TRH in the type of patients studied.     

Assessment of the clinically significant TSH response to TRH in patients with nodular goitre

Twenty-five patients with nodular goitre who had thyroid hormone levels within normal ranges and an absent thyrotropin (TSH) response to TSH releasing hormone (TRH) as measured by a conventional radioimmunoassay with a lower detection limit of 0.6 mU/l were studied. Based on these data, and the clinical evaluation patients were divided into a hyperthyroid group (n = 12) and a euthyroid group (n = 13). The samples from the TRH test were reanalyzed by an immunoradiometric TSH assay with a detection limit of 0.05 mU/l. Basal serum TSH showed a considerable overlap between the two groups, but values above 0.10 mU/l were always associated with euthyroidism. Using this level of discrimination 76% of the patients were correctly classified. A TSH response to TRH of 0.10 mU/l provided a better discrimination allowing a correct diagnosis in 92% of the patients. It is concluded that serum TSH as measured by a sensitive assay is suitable as a first line test in patients with nodular goitre. However, patients with basal serum TSH levels below 0.10 mU/l need further investigation with a TRH-test. A TSH response to TRH above 0.10 mU/l seems to secure euthyroidism, whereas lower responses almost always are associated with hyperthyroidism.     

Oral thyrotropin-releasing hormone (TRH) test in acromegaly

The effects of 40 mg oral and 200 microgram intravenous TRH were studied in patients with active acromegaly. Administration of oral TRH to each of 14 acromegalics resulted in more pronounced TSH response in all patients and more pronounced response of triiodothyronine in most of them (delta max TSh after oral TRh 36.4 +/- 10.0 (SEM) mU/l vs. delta max TSH after i.v. TRH 7.7 +/- 1.5 mU/l, P less than 0.05; delta max T3 after oral TRH 0.88 +/- 0.24 nmol/vs. delta max T3 after i.v. TRH 0.23 +/- 0.06 nmol/l, P less than 0.05). Oral TRH elicited unimpaired TSH response even in those acromegalics where the TSH response to i.v. TRH was absent or blunted. In contrast to TSH stimulation, oral TRH did not elicit positive paradoxical growth hormone response in any of 8 patients with absent stimulation after i.v. TRH. In 7 growth hormone responders to TRH stimulation the oral TRH-induced growth hormone response was insignificantly lower than that after i.v. TRH (delta max GH after oral TRH 65.4 +/- 28.1 microgram/l vs. delta max GH after i.v. TRH 87.7 +/- 25.6 microgram/l, P greater than 0.05). In 7 acromegalics 200 microgram i.v. TRH represented a stronger stimulus for prolactin release than 40 mg oral TRH (delta max PRL after i.v. TRH 19.6 +/- 3.22 microgram/, delta max PRL after oral TRH 11.1 +/- 2.02 microgram/, P less than 0.05). Conclusion: In acromegalics 40 mg oral TRH stimulation is useful in the evaluation of the function of pituitary thyrotrophs because it shows more pronounced effect than 200 microgram TRH intravenously. No advantage of oral TRH stimulation was seen in the assessment of prolactin stimulation and paradoxical growth hormone responses.     

Galactorrhea in subclinical hypothyroidism

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.     

The pituitary-thyroid axis in acromegaly

The pituitary-thyroid axis of 12 acromegalic patients was evaluated by measurement of the serum concentrations (total and free) of thyroxine (T4), triiodothyronine (T3) and reverse T3 (rT3) and thyrotropin (TSH), growth hormone (GH) and prolactin (PRL) before and after iv stimulation with thyrotropin releasing hormone (TRH). Using an ultrasensitive method of TSH measurement (IRMA) basal serum TSH levels of the patients (0.76, 0.07-1.90 mIU/l) were found slightly, but significantly (P less than 0.01), lower than in 40 healthy controls (1.40, 0.41-2.50 mIU/l). The total T4 levels (TT4) were also reduced (84, 69-106 nmol/l vs 100, 72-156 nmol/l, P less than 0.01) and significantly correlated (P less than 0.02, R = 0.69) to the TSH response to TRH, suggesting a slight central hypothyroidism. The acromegalics had, however, normal serum levels of TT3 (1.79, 1.23-2.52 nmol/l vs 1.74, 0.78-2.84 nmol/l, P greater than 0.10), but significantly decreased levels of TrT3 (0.173, 0.077-0.430 nmol/l vs 0.368, 0.154-0.584 nmol/l, P less than 0.01) compared to the controls. The serum concentration of the free iodothyronines (FT4, FT3, FrT3) showed similar differences between acromegalics and normal controls. All the acromegalics showed a rise of serum TSH, GH and PRL after TRH. Positive correlation (P less than 0.05, R = 0.59) was found between the TSH and GH responses, but not between these two parameters and the PRL response to TRH. These findings may be explained by the existence of a central suppression of the TSH and GH secretion in acromegalic subjects, possibly exerted by somatostatin. Euthyroidism might be maintained by an increased extrathyroidal conversion of T4 to T3.     

Ophthalmic Graves's disease: natural history and detailed thyroid function studies.

Of 27 patients with ophthalmic Graves''s disease (OGD) who had been clinically euthyroid three years previously, one became clinically hyperthyroid and seven overtly hypothyroid. Improvement in eye signs was associated with a return to normal of thyroidal suppression by triiodothyronine (T3) and of the response of thyroid-stimulating hormone (TSH) to thyrotrophin-releasing hormone (TRH). Of a further 30 patients with OGD who had not been studied previously, three were overtly hypothyroid. Of the combined series, 46 patients were euthyroid, 18 (40%) of whom had an impaired or absent TSH response to TRH, and 3(6-7%) an exaggerated response. Eleven out of 37 patients (29-7%) had abnormal results in the T3 suppression test. There was a significant correlation between thyroidal suppression by T3 and the TSH response to TRH. Total serum concentrations of both T3 and thyroxine (T4) were closely correlated with T3 suppressibility and TRH responsiveness. Free T4 and T3 (fT3) concentrations were normal in all but three patients, in whom raised fT3 was accompanied by abnormal TSH responses and thyroidal suppression. The presence of normal free thyroid hormone concentrations in patients with impaired or absent TSH responses to TRH is interesting and challenges the concept that free thyroid hormones are the major controlling factors in the feedback control of TSH.     

Maturation of the pituitary-thyroid axis during the perinatal period.

To clarify the maturation process of the pituitary-thyroid axis during the perinatal period, thyrotropin (TSH) response to thyrotropin releasing hormone (TRH) and serum thyroid hormone levels were examined in 26 healthy infants of 30 to 40 weeks gestation. A TRH stimulation test was performed on 10 to 20 postnatal days. Basal concentrations of serum thyroxine (T4), free thyroxine (free T4) and triiodothyronine (T3) were positively correlated to gestational age and birth weight (p less than 0.001-0.01). Seven infants of 30 to 35 gestational weeks demonstrated an exaggerated TSH response to TRH (49.7 +/- 6.7 microU/ml versus 22.1 +/- 4.8 microU/ml, p less than 0.001), which was gradually reduced with gestational age and normalized after 37 weeks gestation. A similar decrease in TSH responsiveness to TRH was also observed longitudinally in all of 5 high responders repeatedly examined. There was a negative correlation between basal or peak TSH concentrations and postconceptional age in high responders (r = -0.59 p less than 0.05, r = -0.66 p less than 0.01), whereas in the normal responders TSH response, remained at a constant level during 31 to 43 postconceptional weeks. On the other hand, there was no correlation between basal or peak TSH levels and serum thyroid hormones. These results indicate that (1) maturation of the pituitary-thyroid axis is intrinsically controlled by gestational age rather than by serum thyroid hormone levels, (2) hypersecretion of TSH in preterm infants induces a progressive increase in serum thyroid hormones, and (3) although there is individual variation in the maturation process, the feedback regulation of the pituitary-thyroid axis matures by approximately the 37th gestational week.     

A case with isolated ACTH deficiency accompanying chronic thyroiditis

An unusual case of isolated ACTH deficiency with coexisting chronic thyroiditis in a 53-year-old man is reported. The patient was admitted with a 2-year history of generalized fatigue, a 13-kg weight loss, muscular weakness, and frequent hypotensive and hypoglycemic attacks. On admission serum thyroxine and triiodothyronine were significantly elevated. Basal TSH concentration was not detected and TSH showed no response to TRH, but one month after replacement therapy with hydrocortisone it was shown that serum T3, T4 and TSH response were all within normal limits. Thyroid antibodies were positive and biopsy of the thyroid gland showed chronic thyroiditis. Arginine and 1-Dopa provoked a subnormal rise in GH with a maximum of 5.6 ng/ml and 5.0, respectively. One month after treatment with hydrocortisone, GH response to 1-Dopa and arginine increased to the normal range. Prolactin response to TRH was normal and FSH response to LHRH was also normal. LH showed an exaggerated response to LHRH, although a normal response was revealed after treatment with hydrocortisone. We also presented a summary of 44 Japanese cases, 23 males (mean age; 46 yrs old) and 21 females (mean age; 48 yrs old), with isolated ACTH deficiency.     

Comparison between the thyrotropin response to thyrotropin-releasing hormone in summer and that in winter in normal subjects.

A comparison was made between the thyrotropin (TSH) response to 500 microgram thyrotropin-releasing hormone (TRH) in summer and that in winter in ten healthy normal adults living in Supporo. The serum resin triiodothyronine (T3) uptake (RT3U), thyroxine (T4) and T3 levels were also measured. While the TSH response to TRH in summer was similar to that in winter, serum T3 concentration and free T3 index were significantly higher in winter than in summer, associated with the similar values in RT3U and T4 levels in serum. Independently measured 86 specimens (43 in summer and 43 in winter) from normal adults living in the same district also showed a significant increase in serum free T3 index as well as a slight elevation of serum T3 concentration in winter but not in serum T4 level. These results indicate that the primary change in cold winter would be the stimulation of peripheral conversion of T4 to T3 rather than the activation of hypothalamo-pituitary-thyroid axis. The relevance of this interpretation was discussed.     

Effect of bromocryptine on the secretion of thyrotropic hormone (TSH), prolactin (Pr), human growth hormone (HGH), thyroxine (T4) and triiodothyroxine (T3) in hypothyroidism.

Bromocryptine (CB-154) virtually abolished the rise of serum Pr after TRH stimulation in hypothyroid and euthyroid subjects. The response of serum TSH to TRH stimulation was significantly depressed in hypothyroid but not in euthyroid subjects. No significant changes of serum HGH, T4 and T3 after CB-154 were observed. The dual mode of action of CB-154 in pituitary and hypothalamus is discussed.     

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.     

Clinical usefulness and limitations of serum thyrotropin measurement by 'ultrasensitive' methods. Comparisons of five kits

Five different ultrasensitive thyrotropin (TSH) assay kits (Boots-Celltech, Immunotech, ORIS-CIS, Travenol and Boehringer) have been used for TSH measurements in various conditions. All the kits were based on an immunometric method but differed with regard to components and procedure. The sensitivity appeared essentially the same for the five kits (0.10 microU/ml) as well as the intraassay precision (coefficient of variation less than 12%). In contrast, the interassay coefficients of variation in the low TSH range varied from 12.8 to 21.3%. Discrepancies from kit to kit were observed and accounted for by differences in the components and procedure of the kits. Basal serum TSH was determined in normal subjects (n = 261) and in patients with thyroid dysfunction (n = 392). No overlap was shown between normals and patients with overt hypothyroidism. In contrast, an overlap existed between normals and hyperthyroids for all the kits but one. Measurements in patients with nontoxic goiter showed that TSH may be undetectable in clinically euthyroid patients, whatever the kit used. After TRH stimulation, 95% of the 375 patients tested associated either an absence of response to TRH with undetectable basal TSH values, or a blunted response with low basal TSH levels or normal response with normal basal TSH concentrations. However, 9 patients with suppressed TSH showed a response to TRH and 7 patients with normal basal TSH levels presented an exaggerated response to TRH. Taken together, these results demonstrate that even though ultrasensitive measurements of TSH do not meet the expectation of completely discriminating euthyroid from hyperthyroid patients, ultrasensitive TSH assay kits represent a powerful tool in the diagnosis of thyroid dysfunction, which would eliminate, in most instances, the need for TRH test and diminish thyroid hormone assay requests.     

Long-term perspectives of thyroxine administration in neonatal rats.

Newborn pups were injected with normal saline (group A) and exogenous thyroxine (group B). Elevated T4 and decreased TSH levels from day 7 in group B continued until day 35. T4 and TSH were in normal range by day 42 and were similar to group A. Weight gain was significantly lower in group B. On day 45, half hourly injections (subcutaneous) of TRH were given to half of group A and group B each. Remaining halves were injected with saline. TSH response to TRH was significantly decreased in group B rats. Thus, neonatal hyperthyroidism results in (1) permanent decrease in pituitary reserve of TSH secretion and (2) a permanent imprinting regarding growth and thyroidal development and thus, neonatal period is critical for thyroidal development.     

Thyroid dysfunction in adult long-term survivors after hemapoeitic stem-cell transplantation (HSCT).

Thyroid function was evaluated in 72 adult survivors (41 females and 31 males) at 16 to 56 years of age, 1.5 years mean time (range 0.2 - 9.8) after hemapoeitic stem cell transplantation (HSCT) with no known prior history of thyroid dysfunction. Thyroid stimulating hormone (TSH) and free thyroxin levels (FT4) were determined before and after stimulation with thyrotropin releasing hormone (TRH). Conditioning regimens for HSCT did not include TBI. Overt hypothyroidism (basal TSH > 8 microIU/ml, FT4 < 0.8 ng/dl) was observed in 6% of male patients and 5% of female patients; subclinical hypothyroidism (basal TSH 4 - 8 microIU/ml, low normal FT4 0.8 - 1.9 ng/dl) was observed in 13% of males and 5% of females. A significant number of euthyroid patients (40% males and 54% females) with normal basal TSH and FT4 levels overresponded to TRH stimulation; the finding being statistically significant (p < 0.005). A heavy TSH response after TRH stimulation indicates compensated subclinical dysfunction of the thyroid gland. Chemotherapy-only conditioning regimens may have an adverse effect on thyroid gland function not always detected by determination of basal TSH and FT4 levels. This finding warrants long-term evaluation of thyroid function in HSCT patients.     

Effect of repeated stimulation by thyrotropin-releasing hormone (TRH) on thyrotropin and prolactin secretion in perfused euthyroid and hypothyroid rat pituitary fragments

The previously reported refractoriness of pituitary response to thyrotropin-releasing hormone (TRH) stimuli was investigated here in an in vitro perfusion system using pituitary tissue from euthyroid and hypothyroid rats. Thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to TRH (28 pmol) were significantly greater in hypothyroid tissue compared with euthyroid. Hypothyroid tissue showed a reduction in response to two consecutive stimuli in both TSH and PRL, however the TSH decline in response was more marked than PRL. Euthyroid tissue showed no significant decline in response to TRH. An increase in the dose of TRH (112 pmol), administered to euthyroid tissue, resulted in increased TSH and PRL response, but no decline in response to sequential stimuli was observed. Three consecutive stimuli by TRH (28 pmol) of hypothyroid tissue resulted in a consistent decline in TSH response. The decline in PRL response only reached statistical significance by the third stimulation. Euthyroid and hypothyroid pituitary tissue was subjected to sequential depolarising stimulation with KCl (50 mumol). Euthyroid tissue showed no decline in response in either TSH or PRL. In hypothyroid tissue only, the decline in TSH response reached statistical significance. This decline in TSH response was significantly smaller than the decline in response observed in hypothyroid tissue stimulated with TRH. Refractoriness of hypothyroid pituitary tissue to repeated TRH stimuli is reported here. Our data suggest that the decline in hormonal response cannot be explained solely on the basis of tissue depletion.     

Effects of cold exposure or TRH on the serum TSH levels in the iron-deficient rat

Normal and iron-deficient rats were exposed to cold at 4 degrees C for 1 hr or 5 hrs and the serum TSH, T3 and T4 levels were compared with those in rats kept at room temperature (20 degrees C). There was a rise in serum TSH, T3 and T4 levels in response to 1 hr and 5 hrs of cold exposure in normal, but not in iron-deficient rats. Although pituitary TSH contents were lower in iron-deficient rats, the increases in serum levels of TSH following administration of TRH were similar in both normal and iron-deficient rats. The results suggest that the inability to respond to cold in iron-deficient rats may be due to a reduction in the release of TRH from the hypothalamus.     

The pituitary-thyroid axis in patients with pituitary disorders

The pituitary-thyroid axis of 12 patients, exposed to transsphenoidal pituitary microsurgery because of nonfunctioning adenomas (6), prolactinomas (3) and craniopharyngioma (1), or to major pituitary injury (1 apoplexy, 1 accidental injury), was controlled more than 6 months following the incidents. The patients did not receive thyroid replacement therapy and were evaluated by measurement of the serum concentration of thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), T3-resin uptake test and thyrotropin (TSH, IRMA method) before and after 200 micrograms thyrotropin releasing hormone (TRH) iv. The examination also included measurement of prolactin (PRL) and cortisol (C) in serum. Apart from 1 patient with pituitary apoplexy all had normal basal TSH levels and 9 showed a significant TSH response to TRH. Compared to 40 normal control subjects the 12 patients had significantly decreased levels of T4, T3 and rT3 (expressed in free indices), while the TSH levels showed no change. Five of the patients, studied before and following surgery, had all decreased and subnormal FT4I (free T4 index) after surgery, but unchanged FT3I and TSH. The levels of FT4I were positively correlated to both those of FT3I and FrT3I, but not to TSH. The TSH and thyroid hormone values showed no relationship to the levels of PRL or C of the patients exposed to surgery. It is concluded that the risk of hypothyroidism in patients exposed to pituitary microsurgery is not appearing from the TSH response to TRH, but from the thyroid hormone levels.     

Influence of D-thyroxine on plasma thyroid hormone levels and TSH secretion.

Triiodothyronine (T3), thyroxine (T4), basal TSH and TSH after stimulation with TRH were determined in healthy subjects and patients treated with D-thyroxine (DT4). After a dosage of 6 mg DT4 the D/L T4 plasma concentration rose about 4-fold 4 hours after application and was only moderately elevated 14 hours later. To achieve constantly elevated T4 levels 3 mg DT4 were applied in the further experiment every 12 hours. The D/L T4 plasma concentration rose 2.5-4-fold and there was a small but significant increase of the D/L T3 plasma concentration. 74 hours after onset of treatment basal TSH was below detectable limits and the increase of TSH 30 min after injection of 200 mug TRH (TRH test) was only about 15% compared to zero time. The time course of TSH suppression was investigated after treatment with DT4 and LT4 (single dosage of 3 mg). TRH-tests were performed before, 10, 26, 50 and 74 hours after the first dosage of D or LT4. There was no difference in the time course of basal TSH and TSH stimulated by TRH. In 10 patients on DT4 long-term therapy, basal and stimulated TSH were found to be below the detectable limits of 0.4 mug/ml. Our results show that (1) plasma half-life of DT4 is less than 1 day, (2) TSH suppression after D and LT4 treatment is very similar, and (3) in patients on long-term DT4 treatment, TSH plasma concentration is below detectable limits even after stimulation with TRH.