Basal Serum Thyroxine Level should Guide Initial Thyroxine Replacement Dose in Neonates with Congenital Hypothyroidism

Objective: Initial high-dose sodium levothyroxine (Na-LT4) (10-15 µg/kg/day) replacement for primary congenital hypothyroidism (CH) is recommended in guidelines. However, high-dose Na-LT4 risks iatrogenic hyperthyroidism. The aim of this study was to investigate the normalizing effect of varying initial doses of Na-LT4 on serum thyroid hormone levels. Methods: Fifty-two patients were analyzed retrospectively. The patients were classified into mild (27/51.9%), moderate (11/21.1%) and severe (14/26.9%) CH, based on initial free thyroxine (fT4) levels. Time taken to achieve target hormone levels was compared within groups. Results: Initial mean Na-LT4 doses for mild, moderate and severe disease were 6.9±3.3, 9.4±2.2 and 10.2±2 µg/kg/day. Serum fT4 levels reached the upper half of normal range (>1.32 ng/dL) in a median of 16, 13 and 16 days in patients with mild, moderate and severe CH with the mean time from initial treatment to first control visit of 14.8±6 days (range 1-36). There was no significant difference in terms of time to achieve target fT4 hormone levels according to disease severity (p=0.478). Seven (25.9%), eight (72.7%) and eight (57.1%) patients experienced hyperthyroxinemia (serum fT4 >1.94 ng/dL) in the mild, moderate, and severe CH groups at the first visit, respectively (p=0.016). Conclusion: Not all patients diagnosed with CH require high-dose Na-LT4. Initial dose of Na-LT4 may be selected on the basis of pre-treatment thyroid hormone levels. Some patients with moderate and severe CH, experienced iatrogenic hyperthyroxinemia even though the dose was close to the lower limit of the recommended range in guidelines. We suggest that lower initial doses may be appropriate with closer follow-up within the first week.

Evaluation of hypothalamic-pituitary function in children following acute bacterial meningitis.

BACKGROUND: Previous studies in adults and case reports in children have shown increased frequency of hypothalamo-pituitary dysfunction after infectious diseases of the central nervous system. The aim of this study was to evaluate the function of hypothalamo-pituitary axis in children with a history of bacterial meningitis. METHODS: Patients diagnosed with bacterial meningitis between April 2000 and June 2011 was included. Baseline and stimulated hormonal tests were performed as required for hormonal evaluations following a diagnosis of meningitis. RESULTS: Pituitary function was assessed following a period of 8-135 months (mean 53 months) after bacterial meningitis. Thirty-seven cases (27 male, 15 pubertal) with mean age of 11.1 ± 4.4 years were included. Mean height SDS was 0.01 ± 1.07 and mean BMI SDS was 0.54 ± 1.15 all patients had a SDS above -2 SD. Baseline cortisol and low dose ACTH stimulation revealed normal adrenal functions in all patients. Gonadotropin deficiency was not detected in any of the pubertal cases. Four cases (10.8%) had low IGF1 and IGFBP3 z-scores (<-2 SD) according to age, sex and Tanner stage, but peak GH response in clonidin test was >10 ng/ml in three of them suggesting neurosecretary dysfunction of GH in these cases. The fourth case has died before the test. No one had TSH deficiency and diabetes insipidus, only one case had mild hyperprolactinemia. CONCLUSIONS: Our findings suggest that hypothalamo-pituitary dysfunction is not as common in childhood as in adulthood. The most remarkable finding was neurosecretary dysfunction of GH in some cases.

Influence of iodine supplementation on serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels in severe iodine deficiency.

Iodine deficiency is an important public health problem worldwide. In addition to severe consequences such as brain damage, developmental delay, deficits in hearing and learning, it also has a negative impact on growth. The negative impact of severe iodine deficiency (SID) on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) was shown previously. In this study we aimed to analyze the impact of iodine supplementation on growth and growth factors of children with SID. One hundred and four children (63 boys and 41 girls) aged 5-15 years participated in the study. Height standard deviation scores (HSDS), and serum levels of IGF-I and IGFBP-3 were assessed both before and six months after a single dose of iodized oil. Serum levels of free thyroxine (FT4) and thyroid stimulating hormone (TSH) were also analysed to investigate the mechanisms by which alterations of iodine status may influence growth. Pubertal children had lower HSDS six months after iodine supplementation, while that of prepubertal children remained unchanged. IGF-I and IGFBP-3 levels decreased significantly and FT4 levels were suppressed six months after the supplementation, while TSH was normalized. These findings suggest a negative impact of iodine supplementation on growth factors in the short-term, which may be a direct effect of iodine repletion or an indirect effect caused by alterations in thyroid function. It may also be related to the method of supplementation used. Further studies are necessary to resolve these issues, as well as to examine the impact of iodine supplementation on growth in the long-term.

Risk factors for vitamin D deficiency in breast-fed newborns and their mothers.

OBJECTIVES: Vitamin D plays a critically important role in the development, growth, and mineralization of the skeleton during its formative years, and performs an equally essential role in maintaining a healthy mineralized skeleton for adults of all ages. We evaluated the vitamin D status and risk factors for vitamin D deficiency in healthy breast-fed newborns and their nursing mothers. METHODS: Serum 25-hydroxyvitamin D (25OHD), calcium, phosphorus, and alkaline phosphatase levels were measured in 54 newborns and their nursing mothers whose ages ranged from 18 to 38 y. The relation between serum 25OHD level and demographic factors was analyzed. Bone mineral density was measured in the mothers with a serum 25OHD level below 25 nmol/L to determine the extent of bone mineralization. RESULTS: The mean serum 25OHD level in the 54 mothers was 29.11 +/- 10.47 nmol/L. Forty-six percent of the mothers had serum 25OHD levels below 25 nmol/L. The risk factors for low maternal serum 25OHD level were found in decreasing order of importance as follows: low socioeconomic class (odds ratio [OR] = 8.1, P = 0.000), being covered (OR = 4.3, P = 0.023), and low educational level (OR = 3.5, P = 0.033). The mean serum 25OHD level in the newborns was 18.62 +/- 8.00 nmol/L. Eighty percent of the newborns had serum 25OHD levels below 25 nmol/L. There was a significant correlation between the serum 25OHD levels of the newborns and their mothers (r = 0.63, P = 0.01). The most important risk factor for low serum 25OHD level in the newborn was a maternal 25OHD level below 25 nmol/L (OR = 15.2, P = 0.002), followed a covered mother (OR = 6.8, P = 0.011). Bone mineral densitometry showed osteopenia in 40% of the women with serum 25OHD levels below 25 nmol/L. All women were from a lower socioeconomic class and 80% were covered. CONCLUSIONS: Vitamin D deficiency is still a common and serious health problem of women of reproductive age and their babies in developing countries at the outset of a new millennium.