Correlates of age at diagnosis of autism spectrum disorders in six Canadian regions.

INTRODUCTION: Early identification of autism spectrum disorders (ASD) is important, since earlier exposure to behavioural intervention programs may result in better outcomes for the child. Moreover, it allows families timely access to other treatments and supports. METHODS: Using generalized linear modeling, we examined the association between child and family characteristics and the age at which 2180 children were diagnosed with ASD between 1997 and 2005 in six Canadian regions. RESULTS: A diagnosis of pervasive developmental disorder-not otherwise specified (PDD-NOS) or Asperger syndrome, rural residence, diagnosis in more recent years, and foreign birthplace were associated with a later age at diagnosis. Children who are visible minorities or who have siblings with ASD were more likely to be diagnosed earlier. Collectively, these factors explained little of the variation in age at diagnosis, however. CONCLUSION: While it is encouraging that ethnocultural identity, neighbourhood income, urban or rural residence, and sex of the child were not major contributors to disparities in the age when children were identified with ASD, more work is needed to determine what does account for the differences observed. Regional variations in the impact of several factors suggest that aggregating data may not be an optimal strategy if the findings are meant to inform policy and clinical practice at the local level.

Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10), hypothyroid (N = 10), treated with 0.05 percent 6-propyl-2-thiouracil (PTU) in drinking water for 60 days, and T4-treated group (N = 10), receiving daily sc injections of L-thyroxine (0.8 æg/100 g body weight) during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71 percent of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72 percent of controls and only in 34 percent of hypothyroid and 43 percent of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed

Is the infertility in hypothyroidism mainly due to ovarian or pituitary functional changes?

The objective of the present study was to examine whether hypothyroidism affects the reproductive system of adult female rats by evaluating ovarian morphology, uterus weight and the changes in serum and pituitary concentrations of prolactin and gonadotropins. Three-month-old female rats were divided into three groups: control (N = 10), hypothyroid (N = 10), treated with 0.05% 6-propyl-2-thiouracil (PTU) in drinking water for 60 days, and T4-treated group (N = 10), receiving daily sc injections of L-thyroxine (0.8 microg/100 g body weight) during the last 10 days of the experiment. At the end of 50 days of hypothyroidism no hypothyroid animal showed a regular cycle, while 71% of controls as well as the T4-treated rats showed regular cycles. Corpora lutea, growing follicles and mature Graafian follicles were found in all ovaries studied. The corpora lutea were smaller in both the hypothyroid and T4-replaced rats. Graafian follicles were found in 72% of controls and only in 34% of hypothyroid and 43% of T4-treated animals. Serum LH, FSH, progesterone and estradiol concentrations did not differ among the three groups. Serum prolactin concentration and the pituitary content of the three hormones studied were higher in the hypothyroid animals compared to control. T4 treatment restored serum prolactin concentration to the level found in controls, but only partially normalized the pituitary content of gonadotropins and prolactin. In conclusion, the morphological changes caused by hypothyroidism can be a consequence of higher prolactin production that can block the secretion and action of gonadotropins, being the main cause of the changes observed.

Menstrual irregularity in the first postmenarchal years: an early clinical sign of polycystic ovary syndrome in adolescence.

We determined the hormonal, metabolic and ultrasonographic pattern of adolescents with menstrual irregularity since menarche but without clinical signs of hyperandrogenism with the aim of evaluating whether this condition represents an early stage of polycystic ovary syndrome (PCOS). These adolescents were divided in two groups: 13 adolescents with irregular cycles (IC) within the first 3 postmenarchal years (IC < or = 3) and 15 adolescents having persistent irregular cycles for more than three postmenarchal years (IC > 3). These adolescents were compared with 15 adolescents with PCOS and 18 normal adolescents. The values of free testosterone, free androgen index, luteinizing hormone (LH) and LH/follicle-stimulating hormone (FSH) ratio were similar in IC < or = 3, IC > 3 and PCOS, and higher than in the normal group (p < 0.005). The total testosterone and androstenedione levels were higher and sex hormone-binding globulin (SHBG) lower in PCOS only when compared with the normal group (p < 0.05). The ovarian volume was similar in IC < or = 3, IC > 3 and PCOS, and higher than in the normal group (p < 0.005). A higher incidence of polycystic structure was found in IC < or = 3, IC > 3 and PCOS, whereas normal structure was more common in normal adolescents (p < 0.0005). There were no significant differences in glucose and insulin parameters between groups. These results indicate that menstrual irregularity within the first postmenarchal years can be an early clinical sign of PCOS.

Nailfold capillaroscopy in hypothyroidism and hyperthyroidism: blood flow velocity during rest and postocclusive reactive hyperemia.

Direct intravital microscopic examinations of nailfold capillaries were made in three groups of subjects: 15 healthy volunteers (C) and 11 patients, six with hypothyroidism (h) and five with hyperthyroidism (H). The groups h and H were examined twice, before the onset of treatment and when they returned to euthyroidism. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60-second arterial occlusion. To assess autoregulatory capacity the authors determined peak CBFV postocclusion and time to reach it in single capillaries. In patients with hypothyroidism, before the onset of the treatment, the mean resting and the mean peak CBFV were significantly lower (resting CBFV-group C: 0.93+/-0.11 mm/s (mean+/-SE); group h: 0.33+/-0.09 mm/s; and mean peak CBFV-group C: 1.49+/-0.14 mm/s; group h: 0.79+/-0.19 mm/s). The time to reach mean peak CBFV postocclusion was significantly prolonged (group C: 8.9+/-0.65 s and group h: 19.2+/-2.0 s) compared with the group of healthy volunteers. When these patients achieved euthyroidism, all the studied parameters returned to control levels. In patients with hyperthyroidism only minor changes in CBFV could be detected. In patients with hypothyroidism, the skin microvascular autoregulatory mechanisms are disturbed. The impairments of the reactive hyperemia response could be correlated with the control of the disease (thyroid state).

Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus.

Short-term experimental diabetes mellitus (DM) produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days), short-term (15 days) and chronic (6 months) streptozotocin-induced diabetes mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 microM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 micrograms/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 micrograms/dl after 15 days of DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary.

Pituitary-thyroid axis in short- and long-term experimental diabetes mellitus

Short-term experimental diabetes mellitus (DM) produces a significant decrease in serum thyroid hormones, a decreased or normal serum thyroid-stimulating hormone (TSH) and a reduction in hepatic and renal T4-5'-deiodination. However, little is known about the effects of chronic diabetes mellitus on the pituitary-thyroid axis function. We evaluated the changes induced by very short-term (6 days), short-term (15 days) and chronic (6 months) streptozotocin-induced diabet mellitus in 3-month old female Dutch-Miranda rat serum T4, serum TSH and T4-5'-deiodinase activity in the thyroid and pituitary glands. Serum hormones were determined by specific radioimmunoassays. Iodothyronine-5'-deiodinase activities were assayed in the thyroid and pituitary microsomal fractions using 2 muM T4 as substrate. Mean serum T4 was significantly decreased from 3.3 to 2.0 mug/dl 6 days after diabetes mellitus induction, and from 2.2 to 1.5 mug/dl after 15 days DM, with no significant changes in serum TSH, indicating a decreased pituitary TSH responsiveness to the diminished suppression by T4, even though pituitary T4-5'-deiodinase activity was unchanged. Thyroid T4-5'-deiodinase was unchanged after 6 days of diabetes mellitus, but was significantly increased from 20.6 to 37.0 pmol T3/mg protein after 15 days. Six months after diabetes mellitus induction, both serum T4 and thyroid T4-5'-deiodinase returned to normal ranges and serum TSH was unchanged, although pituitary T4-5'-deiodinase was now significantly decreased from 2.7 to 1.7 pmol T3/mg protein. These findings indicate that some kind of adaptation to chronic insulinopenia may occur at the thyroid level, but this does not seem to be true for the pituitary.

Nailfold capillaroscopy in non-insulin dependent diabetes mellitus: blood flow velocity during rest and post-occlusive reactive hyperaemia.

Direct intravital microscopic examinations of nailfold capillaries were made in two groups of subjects: 15 healthy volunteers (C) and 16 non-insulin dependent (D II) diabetic patients. In the diabetic group, the disease duration was less than 1 year (n = 4), between 1 and 10 years (n = 8) and between 10 and 18 years (n = 4). Capillary morphology was evaluated and the distribution of morphological patterns was significantly different between the two groups (P less than 0.001). The number of enlarged capillaries was increased in the D II group compared to the C group and capillaries with nodular apical elongations were only found in diabetics. Capillary blood flow velocity (CBFV) was measured during rest and after release of 60 s arterial occlusion. To assess autoregulatory capacity we determined peak CBFV post occlusion and time to reach it in single capillaries. Mean resting CBFV was not statistically different in the two groups but mean peak CBFV post occlusion was significantly lower (C: 1.49 +/- 0.14 mm s-1; mean +/- SE; D II: 0.93 +/- 0.13 mm s-1, P less than 0.05) and mean time to reach it significantly prolonged (C: 8.9 +/- 0.6 s; D II: 18.0 +/- 1.9 s; P less than 0.05) in diabetics compared to controls. Thus skin microvascular autoregulatory responses are disturbed in these patients. The impairments of the reactive hyperaemia response could not be correlated to either metabolic control or duration of the disease.

Lack of correlation between peroxidase activity and iodothyronine levels in human and murine thyroid tissues.

Since thyroid peroxidase (TPO) is essential in thyroid hormone biosynthesis, we evaluated whether a correlation exists between TPO activity and iodothyronine stores in human thyroid tissues from nodular goiters with scintigraphically "cold" (N = 10) or "hot" (N = 7) nodules, diffuse toxic goiters (N = 6), and in normal rat thyroids (N = 18). T4, T3 and rT3 were significantly correlated (rs greater than 0.84, P less than 0.001) in human thyroid tissues, although no correlation between TPO activity and any of the iodothyronines was found. Both TPO and the iodothyronines in human goitrous thyroid glands showed great variation which may mask an underlying relationship. However, this is unlikely since no correlation was found between the much less variable TPO and T4 or T3 in the normal murine thyroid. Other factors related to iodothyronine synthesis and secretion must be at least as important as TPO in determining thyroidal stores.

Thyroid function in fasting rats: variations in 131I uptake and transient decrease in peroxidase activity.

Serum thyroxine and triiodothyronine, radioiodide thyroid uptake and thyroid peroxidase (TPO) activity were studied over a 2 to 5 day period in fasting rats treated (F+) or not (F-) with TSH. In F- rats, TPO activity was transiently decreased on the 3rd day, whereas in F+ it was always higher than in controls. On the 5th day, the 2 h thyroid uptake of 131I decreased in F-, while the 24 h uptake increased in both F- and F+. Serum T3 and T4 decreased in both fasting groups. Thus, not all effects of fasting on rat thyroid function are reverted by TSH administration, suggesting intrinsic impairment of glandular function.

Analysis of thyroglobulins 27S and 19S and their hormonal content in human thyroid glands.

Thyroglobulins (Tg) 27S and 19S and their hormonal content were determined in normal (N = 6), paranodular (N = 4) and hypofunctioning nodular (N = 8) human thyroid tissues. The proportion of Tg 27S and the hormonal content of Tg 19S were significantly decreased in cold nodules. In normal tissues, the molar ratio of T4 in Tg 27S (2.8) was almost twice that found in Tg 19S (1.7), while for T3 the molar ratio in Tg 27S (0.06) was lower than in Tg 19S (0.09). These results indicate that Tg 27S is predominantly formed from well iodinated T4-containing Tg 19S molecules.

Nailfold capillaroscopy in diabetes mellitus: morphological abnormalities and relationship with microangiopathy.

The morphology and density of nailfold capillaries were evaluated in patients with Type I and Type II diabetes mellitus and in healthy controls, using videocapillaroscopy. A protocol of well-defined capillary patterns was used. Diabetic patients had more tortuous and enlarged capillaries than controls. Nodular apical elongation was found only in diabetics and was more frequent in patients with a longer history of disease. Type II diabetic patients with chronic clinical complications had a higher frequency of enlarged capillaries and nodular apical elongation. Glycemic control was without influence. Capillary density did not differ among the groups.

Nailford capillaroscopy in diabetes mellitus: morphological abnormalities and relationship with microangiopathy

the morphology and density of nailfold capillaries were evaluated in patients with Type I and Type II diabetes mellitus and in healthy controls, using videocapillaroscopy. A protocol of well-defined capillary patterns was used. Diabetic patients had more tortuous and enlarged capillaries than controls. Nodular apical elongation was found only in diabetics and was more frequent in patients with a longer history of disease. Type II diabetic patientes with chronic clinical complications had a higher frequency of enlarged capillaries and nodular apical elongation. Glycemic control was without influence. Capillary densitu did not differ among the groups