Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed.     

Thyrotropin-releasing hormone and thyrotropin secretion

Thyrotropin (TSH) secretion is regulated primarily by thyroid hormones and thyrotropin-releasing hormone (TRH). Normally, TSH secretion is exquisitely sensitive to small increases and decreases in serum thyroid hormone concentrations when they occur as a result of alterations in thyroid secretion. Serum TSH responses to TRH are altered by even smaller decreases and increases in serum thyroid hormone concentrations. This sensitivity explains the value of measurements of basal serum TSH concentrations and serum TSH responses to TRH in the diagnosis of hypothyroidism and hyperthyroidism, respectively. How TRH secretion is regulated is unknown, but the direct inhibitory effect of thyroid hormones on the thyrotrophs minimizes the stimulatory effect of any chronic changes in TRH secretion that may occur. In patients with nonthyroid illness, however, the normal relationships between serum thyroxine and triiodothyronine concentrations and TSH secretion are altered. Slightly or moderately ill patients have decreases in extrathyroidal triiodothyronine production that are not followed by an increase in TSH secretion, although the sensitivity of the thyrotrophs to further reduction or to an increase in triiodothyronine concentration is maintained. More severe illness may result in impaired TSH secretion and thus in decreased thyroidal as well as decreased extrathyroidal thyroid hormone production. These alterations in thyrotroph sensitivity and secretion, so that TSH secretion is not increased when extrathyroidal triiodothyronine production is decreased and thyroid secretion is decreased in more severe illness, suggest that decreased thyroid hormone production is a beneficial adaptation to nonthyroid illness.     

Central hypothyroidism and hyperthyroidism

Thyroid function is maintained by tonic secretion of TSH by the pituitary. TSH secretion, in turn, is dependent on hypothalamic TRH production. Therefore, diseases of the hypothalamus and pituitary are frequently associated with TSH deficiency, producing central hypothyroidism. All patients with hypothalamic or pituitary disease should have thyroid function tests including a serum TSH by radioimmunoassay (RIA). In central hypothyroidism the TSH RIA is inappropriately low in relationship to the degree of hypothyroxinemia but is not always undetectable. In fact, because of the production of biologically inactive TSH, the TSH RIA may be in the high range of normal. Therapy of central hypothyroidism includes the management of associated pituitary hormone deficiencies, particularly secondary adrenal failure, and neurologic defects. A rare cause of hyperthyroidism is excessive TSH secretion. This may be due to a TSH-secreting pituitary tumor or to a functional disturbance in TSH secretion. TSH-secreting pituitary tumors are often large and locally invasive. Selective pituitary resistance to thyroid hormone is the most common cause of functional TSH-induced hyperthyroidism. It is important to rule out generalized thyroid hormone resistance before use of antithyroid drugs or thyroid surgery in patients suspected of this disorder. This is because antithyroid treatment is contraindicated in generalized thyroid hormone resistance.     

Clinical utility and cost-effectiveness of sensitive thyrotropin assays in ambulatory and hospitalized patients

In either an ambulatory or a hospitalized patient setting, a normal serum sensitive thyrotropin (TSH) value is strongly suggestive of euthyroidism if the patient has intact hypothalamic-pituitary function and is not receiving drugs known to suppress pituitary TSH secretion. In stable ambulatory patients, an abnormal sensitive TSH value is strongly suggestive of clinical or subclinical thyroid hormone excess or deficiency, which can be confirmed by a free thyroxine (T4) index (FT4I) and evaluation for antimicrosomal antibody (AMA) as a marker of autoimmune thyroid disease. In a hospitalized patient, an abnormality in sensitive TSH or FT4I does not necessarily indicate a thyroid problem but may merely reflect a nonthyroidal illness or glucocorticoid or dopamine treatment. A thyrotropin releasing hormone (TRH) test may be needed to diagnose hyperthyroidism in a hospitalized patient with a basal sensitive TSH level of less than 0.1 microU/ml because a detectable TRH response contraindicates hyperthyroidism whereas hyperthyroid patients with nonthyroidal illness have the expected absent response. In a hospitalized patient, hypothyroidism must be diagnosed on the basis of both a high TSH level and a low FT4I because an isolated high TSH value may merely reflect the recovery phase of a nonthyroidal illness. No clinical urgency exists for establishing a diagnosis of subclinical hypothyroidism in a hospitalized patient; definitive determination of thyroid status can be deferred until recovery and discharge.     

Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin

Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production. The molecular basis of this disorder resides in the dominant inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To determine the relative contributions of pituitary versus hypothalamic resistance to the dysregulated production of thyroid hormone in these patients, we developed a transgenic mouse model with pituitary-specific expression of a mutant TR (Δ337T). The equivalent mutation in humans is associated with severe generalized RTH. Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non–triodothyronine (T₃)-suppressible serum TSH and pituitary TSH-β mRNA. Serum thyroxine (T₄) levels were only marginally elevated in transgenic mice and thyrotropin-releasing hormone (TRH) gene expression in the paraventricular hypothalamus was downregulated. After TRH administration, T₄ concentrations increased markedly in transgenic, but not in wild-type mice. Transgenic mice rendered hypothyroid exhibited a TSH response that was only 30% of the response observed in wild-type animals. These findings indicate that pituitary expression of this mutant TR impairs both T₃-mediated suppression and T₃-independent activation of TSH production in vivo. The discordance between basal TSH and T₄ levels and the reversal with TRH administration demonstrates that resistance at the level of both the thyrotroph and the hypothalamic TRH neurons are required to elevate thyroid hormone levels in patients with RTH.     

Thyrotropin Response to Synthetic Thyrotropin-Releasing Hormone in Normal Subjects and in Patients with Nontoxic Goiter

Abstract. 400 μg TRH given intravenously to normal subjects produced a peak serum TSH within 20 or 30 min. TSH levels were significantly increased as early as 10 min. after the injection. An oral dose of 10 mg of TRH gave a slower and more sustained response in normal subjects. The magnitude of the TSH response was directly related to the basal serum TSH level and inversely proportional to the basal concentration of blood thyroxine. No alteration in the normal pattern of TSH response was observed in patients with euthyroid nontoxic goiters. The data obtained from the normal subjects indicate that the magnitude of the pituitary response to TRH is closely related to the level of the circulating thyroid hormones. Thus, in patients with thyroid pathology the significance of the TSH response curve to TRH must be interpreted after taking into account the level of circulating thyroid hormones. This is particulary important before drawing conclusions concerning any primary defect of the hypothalamo-pituitary system in thyroid pathology.     

Thyroid function after subtotal resection for hyper-thyroidism: a prospective study

B.KÅGEDAL¹
Abstract. Eight-seven patients treated for thyrotoxicosis by subtotal thyroidectomy were examined 6 weeks, 6 months and 12 months after surgery. Thirty-six of the patients were also examined 24 months after surgery.
The patients were divided into two groups according to serum concentration of thyrotrophin (TSH) 6 weeks after surgery. Group I contained fifty-five patients with a normal serum TSH, of whom three developed recurrent hyperthyroidism during the observation period. The remaining fifty-two patients were clinically euthyroid during the entire observation period but had rather low serum thyroxine (T4) levels and normal serum triiodothyronine (T3) levels 6 weeks after surgery. Most patients had a normal TSH response to thyro-trophin-releasing hormone (TRH). T4 levels rose significantly within 6 months after surgery and then remained almost unchanged.
Group II contained thirty-two patients with a serum TSH above 5 mU/1 6 weeks after surgery. Seven of these patients developed hypothyroidism within 1 year of surgery. The twenty-five remaining patients had low serum T4 with normal serum T3 levels at 6 weeks. TSH response to TRH was pathologically raised. Basal TSH level remained raised during the observation period but serum T4 levels approached those in group I within 12 months.
These investigations show that patients with a raised basal serum TSH are at risk of developing hypothyroidism. Normal serum concentrations of thyroid hormones are reached sooner by patients with normal TSH levels than by patients with raised TSH levels. The basal serum TSH level seems to be a better indicator of risk of hypothyroidism than the serum T4 level, which is low in most patients 6 weeks after surgery.     

Use of sensitive immunoradiometric assay for thyrotropin in clinical practice

Although measurement of thyrotropin (thyroid-stimulating hormone; TSH) by radioimmunoassay was a major advance in the laboratory diagnosis of thyroid failure--replacing the time-consuming TSH stimulation test--it was not sufficiently sensitive to discriminate reliably between euthyroid and hyperthyroid patients. Measurement of the TSH response to thyrotropin releasing hormone (TRH) served this purpose, however. The recent development of TSH assays that are severalfold more sensitive and more specific than conventional radioimmunoassays has allowed distinction of euthyroid from hyperthyroid patients and eliminated the need for the TRH test. Although undetectable levels of TSH, compatible with hyperthyroidism, are occasionally noted in euthyroid patients with severe nonthyroidal illness and during the first trimester of pregnancy, false-positive results are less often recorded for TSH than for free or total thyroid hormone measurements. Measurement of TSH by sensitive immunoradiometric assay is currently the most useful first-line test of thyroid function in patients with suspected thyroid disease and, in addition, has a valuable role in monitoring the dose of thyroxine replacement therapy.     

A case of refetoff syndrome: selective venous sampling for TSH is useful in differentiating thyroid hormone resistance from TSH secreting tumor

A 22-year old man with a goiter and clinical manifestations of mild thyrotoxicosis (finger tremor, palpitation, tachycardia) was diagnosed as a syndrome of inappropriate secretion of TSH. Serum concentrations of T4, free T4, T3 and TSH were 24.1 micrograms/100 ml, 4.07 ng/100 ml, 261 ng/100 ml and 1.72 microU/ml, respectively. Thyroidal 131I uptake at 24 hr was 80%. The BMR was within the normal range. He had a normal TSH response to TRH (500 micrograms) with a peak level of 23.8 microU/ml. The basal level of alpha-subunit of TSH was not elevated (0.35 ng/ml). Oral 1-T3 administration (75 and 150 micrograms daily) raised serum T3 concentration, reduced basal TSH and blunted TSH response to TRH. The diurnal variation of TSH was maintained. There was no evidence of abnormalities in the secretion of other pituitary hormones. These findings were compatible with thyroid hormone resistance. However, the presence of a microadenoma in the pituitary gland was suspected with CT scan. Bilateral and simultaneous venous sampling for TSH from inferior petrosal sinus showed no gradient in TSH concentration indicating that a TSH secreting pituitary tumor was unlikely. These data suggest that inappropriate TSH secretion in the present patient is resulted from resistance to thyroid hormone. In the present study selective venous sampling is useful to differentiate the thyroid hormone resistance from a TSH secreting tumor.     

Elderly patients with suppressed serum TSH but normal free thyroid hormone levels usually have mild thyroid overactivity and are at increased risk of developing overt hyperthyroidism.

The clinical and biochemical characteristics of 15 elderly patients with low levels of thyrotrophin (TSH) (< 0.1 mU/L) but normal free tri-iodothyronine (T3) and free thyroxine (T4) (group S) were compared with 10 euthyroid subjects (group E) and 10 hyperthyroid patients (group T). Free T3 and free T4 were significantly higher (p < 0.05) in group S (6.3 +/- 0.5 and 18.6 +/- 1.0 pmol/l, respectively) than in group E (4.6 +/- 0.3, 12.6 +/- 0.6). In common with elderly hyperthyroid patients (group T), patients in group S had few signs or symptoms of thyrotoxicosis, but the Wayne score (clinical index of hyperthyroidism) was higher in group S than in euthyroid subjects (p < 0.05). Thyroid microsomal, thyroglobulin or thyrotrophin receptor antibodies were common in group T (n = 9) but not in groups S (n = 2) or E (n = 1). This suggests a low prevalence of Graves' disease in group S compared to group T. Combined thyrotrophin releasing hormone (TRH; 200 micrograms i.v.) and gonadotrophin releasing hormone (GnRH; 100 micrograms i.v.) tests were performed; no cases of low TSH due to hypopituitarism were identified in group S. During a mean of 7.9 (4-12) months of observation TSH reverted to the normal range (> 0.2 mU/L) in 7 of 15 patients in group S; thyroid hormone concentrations rose above the normal range in four, however, only two patients required treatment for hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Elderly Patients with Suppressed Serum TSH but Normal Free Thyroid Hormone Levels Usually Have Mild Thyroid Overactivity and are at Increased Risk of Developing Overt Hyperthyroidism

The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (4–12)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism.     

Endocrine and reproductive dysfunction following fractionated total body irradiation in adults

The endocrine and reproductive sequelae of total body irradiation for haematological malignancy have been studied in 21 patients (11 male) who were treated with 10 Gy in five fractions or 12 or 13.2 Gy in six fractions over 3 days. Eighteen patients (eight male) aged 16-49 years underwent dynamic tests of the hypothalamic-pituitary axis with insulin hypoglycaemia, thyrotrophin releasing hormone (TRH) and gonadotrophin releasing hormone stimulation and basal measurement of prolactin, sex steroids and thyroid hormones. Growth hormone responses (mean peak 64 +/- 36 mU/l, range 21-146 mU/l) and cortisol responses (mean peak 831 +/- 122 nmol/l, range 626-1105 nmol/l) were all within the normal range. Two patients had minimally elevated serum prolactin levels (445 and 588 mU/l, normal less than 350 mU/l). Serum thyroxine levels (57-133 nmol/l) were normal but six patients had elevated basal thyrotrophin (TSH) levels (6-9 mU/l) and seven had an exaggerated TSH response to thyrotrophin releasing hormone, indicating radiation-induced damage to the thyroid. Amenorrhea developed within 3 months of irradiation in all females and oestradiol levels were low, at 37-108 pmol/l (mean 58 +/- 22 pmol/l). Severe oligospermia or azoospermia was noted in men tested 5-70 months after irradiation and testicular volume was below the normal adult range in five of seven men assessed. Serum testosterone levels (12.4-35 nmol/l) were normal. Gonadotrophin-releasing hormone-stimulated gonadotrophin levels were elevated in all patients. However, two men have fathered two children each; one has refused semen analysis, but the other has a sperm count of 7 x 10(6)/ml (60 per cent motile, 20 per cent abnormal forms) 70 months after irradiation. When given by the above fractionated regimens, the endocrine sequelae of total body irradiation are limited to gonadal failure requiring oestrogen replacement in women and severe impairment of fertility in men. Subclinical thyroid dysfunction has been seen in 39 per cent of patients there is no evidence of direct damage to the hypothalamic pituitary axis.     

The TSH, T4, T3 and prolactin responses to consecutive infusions of a potent and stabilized thyrotrophin releasing hormone analogue, RX77368, in man

The endocrine manifestations of a stabilized thyrotrophin releasing hormone (TRH) analogue, RX77368, have been investigated in six male volunteers. Infusions were given on two occasions, with a 5-day interval between infusions. On the second exposure to RX77368, there was a significant reduction in the TSH response, despite normal basal T3 and T4 levels, while the response of prolactin to RX77368 was unaltered. Domperidone administered during the infusion of RX77368 caused a further elevation of prolactin levels, whilst TSH levels were unchanged. This study shows the differential regulation of thyrotrophs and lactotrophs in response to stimulation by a TRH analogue, and shows, for the first time, down-regulation of the TSH response in vivo, in the presence of normal peripheral thyroid hormone levels. The T3 response to infusions of RX77368 was less than to a bolus injection of TRH, despite a greater TSH response to the analogue, suggesting impaired biological activity of TSH released in response to an infusion of the analogue.     

L-thyroxin treatment in infants with hyperthyrotropinaemia: 4-year experience

Hyperthyrotropinaemia, in which normal levels of T4 occur in association with raised thyroid stimulating hormone (TSH), is usually picked up on neonatal screening. High TSH level can continue for a long time in some of the cases. There is no consensus concerning the follow-up or treatment plan for hyperthyrotropinaemia. In this study, results of a 4-year follow-up of 36 cases who had been medically treated are discussed. Low-dose (5 microg/kg/day) L-thyroxin treatment was carried out in 36 cases that had 5 mU/l or higher TSH and showed exaggerated response to TRH test. Dose was decreased to 2-3 microg/kg/day in 24 of these patients during 6 months follow-up. The drug was stopped in three cases because of the development of biochemical hyperthyroidism. Denver developmental assessment test was applied to all cases at the end of the third year. All patients showed a normal development in relation to their age. According to our results, cases with hyperthyrotropinaemia need to be followed regularly for a long time and a need for low-dose L-thyroxin treatment may exist at ages varying from patient to patient.     

Suppression of Pituitary TSH Secretion in the Patient with a Hyperfunctioning Thyroid Nodule

10 patients with a single hyperfunctioning thyroid nodule each were studied for pituitary thyrotropin (TSH) suppression. They were judged to be euthyroid on clinical grounds. The total thyroxine (T(4)D), free thyroxine (FT(4)), total triiodothyronine (T(3)D), and free triiodothyronine (FT(3)) were normal in most of the patients. Incorporation of (131)I into the hyperfunctioning thyroid nodules was not suppressed by the administration of physiological doses of T(3). Basal serum TSH concentrations were undetectable (<0.5 - 1.0 muU/ml) in all patients. The metabolic clearance of TSH in one patient before and after excision of the thyroid nodule was unchanged (40 vs. 42 ml/min) whereas the calculated production rate was undetectable before the operation (<29 mU/day) and normal after (103 mU/day). These data, in one patient, suggest that the undetectable concentration of TSH in these patients is a result of suppressed TSH secretion rather than accelerated TSH clearance.In eight patients, basal serum TSH concentrations failed to increase after the intravenous administration of 200 mug of thyrotropin-releasing hormone (TRH); minimal increases in serum TSH concentrations were observed in two patients. The suppression of TSH was evident despite "normal" concentrations of circulating thyroid hormones. The observation that normal serum concentrations of T(4)D, FT(4), T(3)D, and FT(3) may be associated with undetectable basal serum TSH concentrations and suppressed TSH response to TRH was also found in four hypothyroid patients given increasing doses of L-thyroxine and sequential TRH stimulation tests.     

Immunoradiometric assay of thyrotropin in plasma: its value in predicting response to thyroliberin stimulation and assessing thyroid function in amiodarone-treated patients

We measured thyrotropin in plasma by an ultrasensitive immunoradiometric assay (TSH-IRMA, "Sucrosep," Boots-Celltech), before and after thyroliberin (TRH) stimulation, in 71 patients with suspected thyroid-function disorders. Thirty-three were taking amiodarone; none was receiving (anti)thyroid drugs. The patients were divided into four groups, according to their TSH response to TRH (as measured previously by conventional TSH-RIA) and the concentrations of thyroxin (T4) and triiodothyronine (T3) in their plasma. Observed ranges of plasma TSH-IRMA (milli-int. units/L) before and after TRH were: euthyroid (n = 20), 0.2-3.0 and 1.7-15.5; subclinically hypothyroid (n = 14), 4.3-18.5 and 20-75; hyperthyroid (n = 17), less than 0.09 and less than 0.09-0.4; and subclinically hyperthyroid (n = 20), less than 0.09-1.1 and less than 0.09-2.6. Evidently TSH-IRMA results for a single sample completely distinguish hyperthyroidism from euthyroidism. However, TSH-IRMA values may also be undetectable in subclinical hyperthyroidism. The TSH response to TRH can be predicted from basal TSH-IRMA results less than 0.09 or greater than or equal to 0.8 milli-int. unit/L, intermediate values can be associated with either a normal TSH response (euthyroidism) or a decreased TSH response (subclinical hyperthyroidism only). We advocate TSH-IRMA as the first diagnostic test of thyroid function for amiodarone-treated patients.     

Thyrotropin-secreting pituitary tumor and Hashimoto's disease: a novel association

A 69-year-old man was referred for elevated thyroid hormone levels. He had no symptoms apart from mild hyperhidrosis and heat intolerance with occasional headaches. Past medical history included a right hemithyroidectomy for a multinodular goiter and Hashimoto's disease. At presentation the patient had a firm, slightly enlarged left thyroid lobe. There were no visual abnormalities, and the rest of the physical findings were unremarkable. Laboratory findings included elevated values of free T4, free T3, total T3, thyrotropin-secreting hormone (TSH), antithyroglobulin, and antimicrosomal antibodies. Normal values were found for cortisol, prolactin, testosterone, follicle-stimulating hormone, luteinizing hormone, alpha-subunit, and thyroid-stimulating immunoglobulin. Thyroid 123I scan showed an increased 5-hour uptake of 23% and a 24-hour uptake of 53% with a diffuse uniform enlargement of the left side. TSH level did not increase after a thyrotropin-releasing hormone stimulation test. Serum sex hormone binding globulin was elevated. Magnetic resonance imaging of the pituitary revealed a pituitary macroadenoma with suprasellar extension to the optic chiasm. Histologic examination of the adenoma after transsphenoidal hypophysectomy showed cells that stained positive for TSH. TSH-secreting pituitary adenomas account for 1% of functioning pituitary tumors and are an exceedingly rare cause of hyperthyroidism. To our knowledge, this is the first report of pituitary tumor inducing hyperthyroidism in the setting of Hashimoto's disease. There is a possibility that TSH elevation related to Hashimoto's disease might have contributed to the development of a TSH-secreting pituitary adenoma.     

Inappropriate TSH secretion with abnormal thyrotroph sensitivity to dopamine

A 47-year-old male schizophrenic with hyperthyroidism was found to have non-neoplastic inappropriate thyrotropin (TSH) secretion. Anterior pituitary function, CT scan and alpha subunit determinations were normal. TSH rose after TRH (7.8 to 22.5 microU/ml) and propylthiouracil (26.1 microU/ml after 3 months) and decreased with oral T3 (Cytomel 25 micrograms po q.i.d.). Cytomel and glucocorticoid infusion blunted but did not completely suppress the TSH response to TRH. Intravenous dopamine infusion (4 micrograms/kg/min) completely suppressed the prolactin but not the TSH response to TRH. The association of schizophrenia and differential thyrotroph sensitivity to dopamine suggests a possible role for dopamine in the pathogenesis of selected cases of non-neoplastic inappropriate TSH secretion.     

糖尿病患者下丘脑-垂体-甲状腺功能临床观察

目的 :观察糖尿病患者下丘脑 垂体 甲状腺功能改变。方法 :检测 5 4例糖尿病患者血糖、甲状腺激素水平及TSH对TRH兴奋试验的反应。结果 :5 4例患者中 2 1例呈低T3血症 ,其中 3例伴有T4水平下降 ,2例伴FT3、FT4下降 ,但T4水平正常。TRH兴奋试验均正常。低T3血症组患者空腹血糖值与基础T3(r=- 0 .5 33,P <0 .0 5 )、基础TSH(r=- 0 .4 88,P <0 .0 5 0 )呈负相关。结论 :糖尿病患者在控制不良或合并严重并发症时呈现低T3综合征 ,但垂体 甲状腺轴的功能正常。检测甲状腺激素水平有助于糖尿病病情及预后的估计。     

Serum Thyrotropin Responses to Synthetic Thyrotropin-Releasing Hormone in Normal Children and Hypopituitary Patients. A NEW TEST TO DISTINGUISH PRIMARY RELEASING HORMONE DEFICIENCY FROM PRIMARY PITUITARY HORMONE DEFICIENCY

Synthetic thyrotropin-releasing hormone (TRH) was administered intravenously in a dose of 7 mug/kg to 20 normal children ages 4-13 yr. Serum thyroid-stimulating hormone (TSH) was measured by radioimmunoassay and rose from a mean value of 1.7 muU/ml (range = < 1.25-7.2) to a mean peak value of 21.5 muU/ml (5.2-33.2) at 15 or 30 min after administration.13 patients with idiopathic hypopituitarism and apparent normal thyroid function, ages 3-19 yr, responded to TRH in a manner very similar to the control subjects: TSH rose from a mean value of 1.8 muU/ml (range < 1.25-4.3) to a mean peak value of 18.5 muU/ml (range = 9.5-45.0) which occurred between 15 and 60 min after TRH.13 idiopathic hypopituitary patients with documented thyroid deficiency were tested after thyroid therapy had been discontinued for a minimum of 10 days. The serum TSH values in 10 of 13 patients rose from a mean base line level of 2.2 muU/ml (< 1.25-5.3) to a peak mean value of 32.5 muU/ml (9.6-61.3) between 30 and 120 min after TRH. In three patients, however, little or no TSH response was detected, even when serum thyroxine levels were extremely low. Similar to the latter group, three of five patients with hypopituitarism secondary to craniopharyngiomas had undetectable or barely measurable TSH levels before and after TRH. Two of these five patients had significant responses which were compatible with hypopituitarism resulting from damage to the hypothalamus or hypothalamic vessels instead of the pituitary.Side effects were experienced in 41 of 54 patients (76%). The effects were limited to a mild nausea-like sensation in 63% of the patients and occurred within the first 5 min after receiving TRH. No evidence of serious toxicity or long-term side effects was noted.The TRH test is a safe, effective way to measure TSH reserve in children. The positive response in 10 of 13 patients with secondary hypothyroidism supports data previously accumulated that most patients with idiopathic hypopituitarism have an abnormality of their hypothalamic-releasing hormone function, whereas the remaining minority probably have primary pituitary disease.