Thyroid function tests in children with congenital hypothyroidism on L-thyroxine treatment

The plasma levels of thyroxine (T4), triiodothyronine (T3), free T4 (FT4), free T3 (FT3), reverse T3 (rT3) and immunoradiometrically assayed thyrotropin (IRMA TSH) have been measured in 28 L-T4-treated children with congenital hypothyroidism as well as in a control group (group C). The patients were subdivided into 2 groups according to the nonsuppressed (group A) or suppressed (group B) TSH response to TSH-releasing hormone (TRH). Basal IRMA TSH correlated with the TSH increment after TRH and it was significantly lower in group B vs. groups A and C, while no difference was present between groups A and B in regard to T4, FT4 and rT3, all higher than in group C. FT3 levels were similar in the 3 groups. In children, as in adults, basal IRMA TSH seems to be a reliable index in monitoring overtreatment.     

Anomalies in thyroid function in children with trisomy 21

Thyroid function of 60 children with Down (DS) aged 3 months to 16 years was studied by evaluation of serum concentration of ultra-sensitive thyroid stimulating hormone (TSH), free T4 and T3 (FT4, FT3), total T4 and T3 (T4 and T3) and reverse T3 (rT3). Each DS child was matched to a control of the same age. The concentration of TSH was increased in DS children while the concentration of rT3 of the DS children was significantly decreased compared to the controls as was the ratio rT3/TSH. These results showed that thyroid function of DS children is abnormal.     

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.     

Changes in circulating iodothyronines in diabetics with various degrees of metabolic control

Plasma TSH, total and free T3 and T4, reverse T3, blood pH, HbAlc, ketonuria and glycosuria were evaluated in 8 subjects with diabetic ketoacidosis, in 54 diabetics of group 1 and group 2 without severe metabolic derangement and in 10 control women. The diabetics with ketoacidosis showed before intensive therapy low T3, total and free, and high reverse T3 concentrations as compared to controls (unpaired t-test, p less than 0.001). After one day of intensive therapy the decrease of hyperglycemia and pH increase (p less than 0.001, paired t-test), glycosuria and ketonuria are not related to significant variations of iodothyronines and TSH. The significant variations (paired t-test, p less than 0.001) in total and free T3 and in reverse T3 concentrations were found only six days after remission of ketoacidosis. In diabetics (type 1 and 2) without recent history of ketoacidosis no differences were found in mean total and free T3 and T4, in reverse T3 and in plasma concentrations although mean blood glucose and HbAlc were statistically different (t-test, p less than 0.001). The changes in serum T3 (total and free) and reverse T3 are useful indicators of total metabolic control during the management of diabetic ketoacidosis.     

Changes in the hypothalamic-pituitary-thyroid axis during acute starvation in non-obese patients

We investigated changes in the hypothalamic-pituitary-thyroid axis before, during, and after fasting in twenty-one non-obese euthyroid patients with psychosomatic diseases. Blood samples for free T3 (FT3), T3, free T4 (FT4), T4, reverse T3 (rT3), and TSH were obtained from all patients before and on the 5th day of fasting, and in 11 of the same individuals on the 5th day of refeeding. Serum TSH and T3 responses to TRH were also evaluated in 10 patients before and on the 5th day of fasting. During the fast, FT3, T3 and TSH levels decreased significantly and rT3 levels increased significantly whereas FT4 and T4 levels remained within the normal range. Maximal delta TSH, peak TSH levels, max delta T3, peak T3 levels, and net secretory responses to TRH decreased significantly. Peak TSH levels and max delta TSH to TRH correlated well with basal levels of TSH. A statistically significant negative correlation between basal levels of FT4 and TSH was observed. After refeeding, there was a significant increase only in TSH which returned to prefasting values. These results demonstrated that in a state of "low T3" during acute starvation a reduction in serum T3 might depend partly on TSH-mediated thyroidal secretion.     

Cardiopulmonary bypass: a low T4 and T3 syndrome with blunted thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH)

Thyroid hormone serum concentrations, the thyrotropin (TSH) and prolactin (PRL) response to thyrotropin-releasing hormone (TRH) were evaluated in patients undergoing cardiopulmonary bypass (CPB) conducted in hypothermia. During CPB a marked decrease of thyroxine (T4) and triiodothyronine (T3) concentration with a concomitant increase of reverse T3 (rT3) were observed similarly to other clinical states associated with the 'low T3 syndrome'. Furthermore, in the present study elevated FT4 and FT3 concentrations were observed. In a group of patients, TRH administered during CPB at 26 degrees C elicited a markedly blunted TSH response. In these patients, PRL concentration was elevated but did not significantly increase after TRH. The increased concentrations of FT4 and FT3 were probably due to the large doses of heparin administered to these patients. Thus, the blunted response of TSH to TRH might be the consequence of the elevation of FT4 and FT3 in serum, however, other factors might play a role since also the PRL response to TRH was blocked.     

Serum TSH, T4, T3, FT4, FT3, rT3, and TBG in youngsters with non-ketotic insulin-dependent diabetes mellitus

Several parameters of thyroid function were studied in 112 non-ketoacidotic youngsters with insulin-dependent diabetes mellitus (IDDM). Levels of thyroxine (T4), reverse triiodothyronine (rT3), thyroxine-binding globulin (TBG) and T3 were lower than in controls, whereas FT4, and FT3 were normal. T4 levels in IDDM patients were positively related to T3, rT3 and TBG, and inversely related to haemoglobin A1 (HbA1). However, only 4 patients showed biochemical hypothyroidism (T4 less than 5 micrograms/100 ml), whereas their FT4, FT3 and thyroid-stimulating hormone (TSH) levels were normal. Concurrent variations of T3 and rT3 levels were found in IDDM patients; thus, their T3/rT3 ratios were stable or higher than in controls, indicating that peripheral deiodination of T4 is preferentially oriented to production of rT3 only during ketoacidosis. Although changes in thyroid function may reflect the degree of metabolic control of diabetes in a large population, the clinical usefulness of serum thyroid hormone measurements in an individual case still appears to be limited.     

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.     

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.     

Effects of TRH on gastric acid secretion: A model for human study

The possible effects of TRH administration on different parameters of gastric function were studied in 10 patients with different gastrointestinal complaints. Basal (BAO) and pentagastrin stimulated (6 μg pentagastrin/kg bw sc) maximal (MAO) acid output were determined and serum levels of TSH, total and free thyroxine (T4 and FT4), triiodothyronine (T3) were measured. After determinations of BAO and MAO and the hormones indicated above, one group of patients received a TRH injection (0.2 mg protirelin) intravenously. The second group of patients was injected with atropine (atropinum sulfuricum, 1 mg, iv). At different times following the injections in both groups of patients BAO, MAO and serum levels of TSH, total and free T4, T3, gastrin were determined. Injection of TRH resulted in an increase in TSH and with some delay in thyroxine and gastric acid levels. Atropine treatment was followed by a decrease in gastric acid secretion and a small decrease in TSH and no changes in the values of the other studied hormones. The results suggest a complex interrelationship between TRH, vagal system and pentagastrin-dependent gastric acid secretion operating in human subjects.     

Serum thyrotropin response to thyrotropin-releasing hormone and free thyroid hormone indices in patients with familial thyroxine-binding globulin deficiency.

The response in serum thyrotropin (TSH) to synthetic thyrotropin-releasing hormone (TRH) as well as serum free thyroxine index (FT4I) and free triiodothyronine index (FT3I) was investigated in six patients with familial thyroxine-binding-globulin (TBG) deficiency. The total serum thyroxine (T4) and triiodothyronine (T3) concentrations were significantly decreased, compared with those of normal subjects (3.4 +/- 0.9 microgram/dl, mean +/- SD. vs. 9.0 +/- 1.5 microgram/dl, p less than 0.01 and 87 +/- 27 ng/dl vs. 153 +/- 37 ng/dl, p less than 0.01, respectively). FT4I was lower than the normal range in all but one (5.3 +/- 1.5 vs. 8.9 +/- 1.6, p less than 0.01), whereas FT3I was all in the normal range and of no significant difference from the normal control (132 +/- 22 vs. 148 +/- 25). Serum TSH concentrations in TBG deficiency were all in the normal range (1.0-4.2 muU/ml) and the maximum TSH increments following TRH 500 microgram iv were 8.9 +/- 2.0 muU/ml and of no significant difference from the normal control (10.2 +/- 4.5 muU/ml). These results indicate that the euthyroid state in familial TBG deficiency is more clearly defined by TRH-test and the normal response to TRH in familial TBG deficiency is presumably under the control of the serum free T3 level rather than the serum free T4 level.     

Behavior of thyroid hormones and TSH in chronic active hepatitis

The authors studied total and free circulating thyroid hormones, rT3, TBG and TSH behaviour on chronic liver disease in 11 subjects with cirrhosis of the liver with ascites(C.E.) and in 6 subjects with chronic active hepatitis (E.C.A.) in comparison with 15 healthy and euthyroid controls. Serum T3,FT3,T4 and FT4 levels were decreased significantly and serum rT3 values increased significantly both in the subjects with C.E. and in patients with E.C.A. Moreover no significantly changes of TSH and TBG levels has been found in 3 groups studied. These data suggest that the alteration of circulating thyroid hormones in chronic liver disease, may represent a compensatory way of reducing the patient's metabolic requirements.     

Effects of streptozotocin-induced diabetes mellitus on hypothalamic-pituitary-thyroid axis in rats

The effects of streptozotocin-induced diabetes mellitus on the hypothalamic-pituitary-thyroid axis in rats were studied. Streptozotocin (60 mg/kg) was injected ip. Rats were decapitated at two and four weeks after the streptozotocin treatment. Thyrotropin releasing hormone (TRH), thyrotropin (TSH), thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) were measured by means of the specific radioimmunoassay for each. Immunoreactive TRH (ir-TRH) contents in the hypothalamus significantly decreased at four weeks (p less than 0.02). Basal TSH levels in plasma significantly decreased (p less than 0.005, p less than 0.001), and plasma ir-TRH and TSH responses to cold were significantly inhibited after the streptozotocin treatment (p less than 0.001). The plasma TSH response to TRH was decreased, but not significantly. The plasma T4 and T3 levels fell significantly. RT3 did not change throughout the experiment. 3,3'-T2 levels in plasma fell significantly, whereas 3',5'-T2 increased. Blood glucose levels rose significantly after streptozotocin treatment, but insulin treatment led to partial restoration. The findings suggest that streptozotocin-induced diabetes mellitus affects various sites of the hypothalamic-pituitary-thyroid axis in rats.     

A case of diabetic non-ketotic hyperosmolar coma with an increase with plasma 3-hydroxybutyrate.

We have seen a case of "diabetic non-ketotic hyperosmolar coma" with ketosis. An 84-year-old man was brought into the hospital in a deeply comatous and dehydrated state. The initial blood glucose level was 1252 mg/dl with plasma osmolarity of 435 mOsm/l, but no ketonuria was detected by the nitroprusside method (Ketostix). However, the plasma 3-hydroxybutyrate (3-OHBA) level was 5 mM in a newly developed bedside film test. The serum ketone bodies were later found to be 5.56 and 0.82 mmol/l for 3-OHBA and acetoacetate (AcAc), respectively. A marked increase in glucagon, cortisol and ADH with renal dysfunction (creatinine 5.0 mg/dl) were noted. An abnormal electrocardiogram, occular convergence and chorea like movement disappeared after correction of metabolic disturbances. The moderate level of IRI (14 microU/ml) on admission and a good response to glucagon 2 months after admission also indicate that the present case is a typical hyperosmolar non-ketotic coma. Because of a preferential increase in 3-OHBA, ketonuria seemed to be absent in the regular nitroprusside test. Marked dehydration is thought to cause renal dysfunction, and the increase in ADH may have helped to prevent further aggravation of ketoacidosis. We propose to change the term hyperosmolar non-ketotic coma (HNC) to diabetic hyperosmolar coma (DHC), because sometimes patients with hyperosmolar non-ketotic diabetic coma are ketotic, as seen in the present case. Determination of 3-OHBA or individual ketone bodies in blood is important and essential for the differential diagnosis of diabetic coma. The diagnosis of either ketoacidotic or hyperosmolar coma should be made depending on the major expression of ketoacidosis or hyperglycemic hyperosmolarity.     

肝病患者血清甲状腺相关物质的检测与意义

目的探讨不同程度肝病患者血清甲状腺激素水平的变化及其意义。方法应用放射免疫法分别检测114例慢性肝炎、130例肝硬化、96例重型肝炎、120例健康体检者的血清甲状腺激素水平(T3、T4、FT3、FT4、rT3、TSH),抗甲状腺过氧化物酶抗体(抗TPO)、抗甲状腺球蛋白抗体(抗TG)的含量变化。结果肝病患者较正常人血清甲状腺素水平(T3、T4、FT3、FT4)显著降低,而抗TPO、抗TG、rT3含量显著升高,差异有统计学意义;随着肝功能受损程度的加重,血清甲状腺素水平(T3、T4、FT3、FT4)降低程度差异有统计学意义。结论肝病患者血清甲状腺激素水平的检测对评估肝功能、判断病程及预测预后有一定的临床意义。     

Pituitary-thyroid axis sensitivity and neonatal changes in plasma iodothyronine, thyreostimulin and cortisol levels in the preterm lamb: comparison of two experimental models

The influence of a 7 days prematurity, induced by oestrogen or dexamethasone injection to the mothers, on neonatal changes in plasma T4, T3, reverse T3 (rT3), TSH and cortisol levels was studied in 6 full term, 6 oestrogen preterm and 6 dexamethasone preterm lambs. In addition, the pituitary-thyroid axis sensitivity was assessed by the magnitude of the response to TRH administration. At birth, plasma cortisol and T3 levels, as the value of the T3/T4 ratio, were significantly lower in the two groups of preterm lambs than in full term animals; however, whereas plasma T3 concentrations and values of the T3/T4 ratio remained low in oestrogen lambs, they were quickly restored and elevated T3 levels associated to high T4 levels could be even observed in dexamethasone lambs; in this last group, these abrupt changes could be a consequence of raised TSH plasma concentrations recorded at birth. Moreover, if plasma rT3 levels and values of the rT3/T4 ratio were similar during the first hours of life in dexamethasone and full-term lambs, they were significantly higher in oestrogen animals. The responsiveness of the pituitary-thyroid axis to TRH was normal in dexamethasone animals, but was significantly enhanced in oestrogen ones, probably as a consequence of low T3 levels.     

Plasma renin activity in diabetic patients.

Plasma renin activity (PRA) in 40 diabetic patients and 42 healthy controls was investigated using the method of Pickens in modification of Serebrovskaja et al. (1967). PRA was slightly lower in the whole group of diabetes but the difference was not significant. The subgroup of 20 maturity-onset diabetics had significantly lower PRA in comparison with 22 controls of similar age, while PRA in juvenile diabetics did not differ significantly from matched controls. In patients without clinical signs and symptoms of microangiopathy PRA was as high as in the controls. In diabetics with microangiopathy PRA was significantly lower. PRA was also lower in patients with longer duration of the disease. The stimulation of juxtaglomerular apparatus with sodium free diet and diuretic drugs resulted in an increase of PRA both in controls and diabetics. This suggests a functional depression of PRA in diabetic patients. In diabetics with ketoacidosis PRA was higher than in control subjects and decreased after disappearance of ketoacidosis. A high level was recorded in a patient with hyperosmolar coma and a very low level in a patient with polyneuropathy and severe orthostatic hypotension. The possible mechanisms involved in the changes of PRA in diabetic patients are discussed.     

Prolactin and thyrotropin response to thyrotropin-releasing hormone in premenopausal women with fibrocystic disease of the breast

Plasma PRL, TSH, total and free T4, total and free T3, and 17 beta-estradiol were evaluated in 29 premenopausal women with well-documented fibrocystic disease of the breast and in 29 healthy matched controls. Plasma PRL and TSH dynamics after acute TRH injection (200 micrograms i.v.) were also determined. All hormonal measurements were performed in the follicular phase of the menstrual cycle. Neither patients nor controls showed any thyroid function impairment. Basal plasma levels of the examined hormones were in the normal range in both groups. When considering data pertinent to PRL and TSH secretory patterns after TRH stimulation, no difference was recorded between patients and controls for TSH secretion, evaluated in terms of maximum peak, net (delta) and percent (delta %) increase above the baseline level and integrated area of response. On the contrary, the response of PRL was significantly higher in patients than controls (maximum peak at 20 min, mean +/- SE, 119.9 +/- 14.1 vs. 60.8 +/- 5.5 ng/ml, p less than 0.001; integrated area of response, 5,725 +/- 908 vs. 3,243 +/- 266 ng/ml/120 min, p less than 0.01). The results are compatible with the view that, in most patients with fibrocystic disease of the breast, there are abnormalities in the control of PRL secretion, which lead to enhanced release of the hormone after stimulation. In such cases the control of TSH appears to be operating normally.     

Thyroid functions in patients with various chronic liver diseases

In order to clarify an alteration in thyroid functions in patients with chronic liver diseases, serum total and free thyroxine (T4, FT4), total and free triiodothyronine (T3, FT3), total reverse T3 (rT3), thyrotropin (TSH), thyroxine-binding globulin (TBG) concentrations, and T3 uptake (T3U) were measured by radioimmunoassays in 53 patients with chronic hepatitis (CH), 24 patients with compensated liver cirrhosis (LC), 17 patients with hepatocellular carcinoma associated with LC (HCC), and 40 normal subjects. Serum T4, T3, and rT3 in CH, and serum rT3 in HCC were significantly increased, while serum T4 in LC and serum T3 in HCC were significantly decreased. Serum TBG was increased and T3U was decreased in these patients. Serum TBG in CH and LC correlated positively with transaminase, and inversely with prothrombin time. FT4 and T4/TBG ratios in CH and LC and FT3 and T3/TBG ratios in LC and HCC were significantly decreased. Although T4/TBG ratios in HCC and T3/TBG ratios in CH were significantly decreased, FT4 in HCC and FT3 in CH were not decreased. The ratio of rT3/T3 in CH and LC correlated with various liver function tests. FT3 in LC and HCC correlated inversely with BSP (45') and positively with KICG. No differences in serum TSH values were found between chronic liver diseases and normal subjects. From these results, it was concluded that the thyroid functions in patients with chronic liver diseases were affected by the decrease in serum thyroxine, elevated serum TBG, the degree of which is in proportion to that of the liver cell damage, and impaired peripheral conversion of T4 to T3, the degree of which is in proportion to that of the hepatic dysfunction.     

Low serum allopregnanolone levels in girls with precocious pubarche

Allopregnanolone, a neuroactive steroid, increases during pubertal development and high concentrations are present in subjects with precocious puberty. The aim of the present study was to evaluate serum allopregnanolone levels in girls with precocious pubarche (PP). Basal gonadotropins and steroid hormones were assessed in 17 girls with PP, 22 girls with central precocious puberty (CPP), 25 girls with normal puberty at the same pubertal stage of CPP ones, and 17 prepubertal girls. Adrenocorticotropin hormone (ACTH) and gonadotropin-releasing hormone (GnRH) stimulation tests were performed in all subjects with PP, and in 12 out of 22 with CPP. All girls with normal puberty underwent to GnRH test, while ACTH test was performed in 17 out of 25. Basal dehydroepiandrosterone sulfate (DHEAS) concentrations resulted significantly higher in PP and normal pubertal girls than in prepubertal ones. Allopregnanolone, gonadotropins and estradiol levels were significantly lower in PP group with respect to CPP (P<0.05), while they were comparable among PP, normal pubertal and prepubertal groups. After ACTH administration, allopregnanolone concentrations significantly increased in all groups (P<0.05). After GnRH stimulation, its levels significantly increased in CPP and normal pubertal controls (P<0.05), while no incremental rise was found in PP girls. In conclusion, our study shows that in girls with PP basal and GnRH-stimulated levels of allopregnanolone are significantly lower than in CPP girls. These data suggest that this neurosteroid may be considered a new marker of pubertal development.