Recombinant growth hormone improves growth and adult height in patients with maternal inactivating GNAS mutations.

BACKGROUND: Maternal inactivating GNAS mutations lead to pseudohypoparathyroidism 1A (PHP1A), newly classified as inactivating parathyroid hormone (PTH)/PTHrP-signaling disorder type 2 of maternal inheritance (iPPSD2). Patients present with resistance to PTH and other hormones, subcutaneous ossifications, brachydactyly, short stature, and early-onset obesity. They can be born small for gestational age (SGA) and may present with growth hormone (GH) deficiency. The use of recombinant human GH (rhGH) therapy has been sporadically reported, yet we lack data on the long-term efficacy and safety of rhGH, as well as on adult height. OBJECTIVE: Our multicenter, retrospective, observational study describes growth in patients treated with rhGH in comparison with untreated iPPSD2/PHP1A controls. METHODS: We included 190 patients, of whom 26 received rhGH. Height, weight, body mass index at various time points, and adult height were documented. We analyzed the effect of rhGH on adult height by using linear mixed models. RESULTS: Adult height was available for 11/26 rhGH-treated individuals and for 69/164 controls. Patients treated with rhGH showed a gain in height of 0.7 standard deviation scores (SDS) after 1 year (CI +0.5 to +0.8, P < .001) and of 1.5 SDS after 3 years (CI +1.0 to +2.0, P < .001). Additionally, there was a clear beneficial impact of rhGH on adult height when compared with untreated controls, with a difference of 1.9 SDS (CI +1.1 to +2.7, P < .001). Body mass index SDS did not vary significantly upon rhGH therapy. CONCLUSION: Recombinant human growth hormone treatment of iPPSD2/PHP1A patients with short stature improves growth and adult height. More studies are needed to confirm long-term efficacy and safety.

Thyroid function in 76 sick preterm infants 30-36 weeks: results from a longitudinal study.

AIM: To assess thyroid function in 76 sick preterm infants 30-36 weeks gestational age. PATIENTS AND METHODS: Measurement of serum TSH, T4, T3, free T4 and rT3 in the mother and cord at delivery, and in the infant at 1 and 24 hours, 1 and 3 weeks, 2, 4, 6 and 12 months of postnatal age. These values were compared with those of 75 healthy age-matched controls. Gestational age was 30 weeks in 24, 31 weeks in 23, 32 weeks in 13, 33 weeks in 13, 34 weeks in one, 35 weeks in one and 36 weeks in one. Hypothyroxinemia at each postnatal age was defined as serum free T4 values under -2 SD of the mean of controls. RESULTS: Forty-four patients were normothy-roxinemic at all times, and 32 presented hypothyroxinemia at 24 hours (29 patients), 1 week (seven patients) and 3 weeks (two patients). Follow-up of 31 patients who were normothyroxinemic at 24 hours of life showed that at one week three (9.7%) were hypothyroxinemic and at 3 weeks all were normothyroxinemic. At 24 hours of life, all patients with patent ductus arteriosus and all patients treated with dopamine were in the hypothyroxinemic range. CONCLUSION: Hypothyroxinemia may be present in sick preterm infants 30-36 weeks of gestational age, particularly in those treated with dopamine and/or presenting patent ductus arteriosus.

Thyroid function in preterm infants 27-29 weeks of gestational age during the first four months of life: results from a prospective study comprising 80 preterm infants.

AIM: Assessment of thyroid function in preterm neonates (PTN) 27-29 weeks of gestational age. PATIENTS AND METHODS: 80 PTN, gestational age 27 weeks in 24, 28 weeks in 28, and 29 weeks in 28. Neonates were classified as healthy (n=17) or sick (n=63). Measurement of serum TSH, free T4, T4, T3 and rT3 in the mother and in the cord at the time of delivery, and in the infant at 1 hour, 24 hours, 1 week, 3 weeks, and 2 and 4 months of postnatal age. RESULTS: In healthy and sick preterms, TSH values peaked at 1 hour and decreased thereafter. Healthy PTN presented a peak in free T4 values at 24 hours that was not observed in sick neonates. Sick PTN had a lower TSH peak and lower free T4 values at 24 hours and 1 week than healthy ones (p < 0.05). Healthy PTN 27-29 weeks had lower TSH peak at 1 hour and lower free T4, T3 and T4 values during the first 2 months than healthy PTN 30-35 weeks (PTN30-35w) previously evaluated (p < 0.05). However, at all postnatal times healthy preterms had free T4 values above -2 SD of the mean values of healthy PTN30-35w. A wide range of free T4 values was observed in the sick group. Free T4 values above -2 SD of the mean values of healthy PTN30-35w were detected in a high proportion of sick PTN (58.3% at 24 hours, 73.5% at 1 week, 93.9% at 3 weeks, 85.1% at 2 months and 100% at 4 months). CONCLUSIONS: Prematurity and disease influence thyroid function, and consequently thyroid function should be individually assessed in preterms 27-29 weeks of gestation during the first 2 months of life.

Thyroid function in seventy-five healthy preterm infants thirty to thirty-five weeks of gestational age: a prospective and longitudinal study during the first year of life.

Thyroid function was evaluated in 75 healthy preterm infants, 30-35 weeks of gestational age. Serum thyrotropin (TSH), thyroxine (T(4)), triiodothyronine (T(3)), free T(4) (immunochemoluminescence) and reverse triiodothyronine (rT(3)) (radioimmunoassay) were measured in the mother and in the cord at delivery and in the preterm infants at 1 hour, 24 hours, 1 week, 3 weeks, 2 months, 4 months, 6 months, and 12 months of postnatal age. These values were compared to those of healthy full-term infants of the same postnatal age (22 at 24 hours from our hospital and from previously reported data at others times). Mean 24-hour TSH values were significantly lower (p < 0.001) in preterm than in full-term infant populations (12.38 +/- 6.13 microIU/mL versus 22.02 +/- 13.28 microIU/mL); however, all TSH values of preterm infants were in the range of the full-term values. Mean 24-hour free T(4) values were similar in preterm and full-term infants (1.88 +/- 0.46 ng/dL versus 2.01 +/- 0.54 ng/dL) and all preterm infants had free T(4) values within the range of those of full-term infants at 24 hours. Mean T(4) and T(3) values were significantly lower in preterm than in full-term neonates at 1 hour and 24 hours of age. Mean 24-hour rT(3) values were significantly higher in preterm than in full-term newborns. From 1 week onwards, all thyroid function values were in the same range in both populations. In conclusion, individual thyroid function was similar in healthy preterms and full-terms from the first 24 hours of life. Normative data in preterm infants during the first year of life applying the latest luminescence techniques currently used worldwide are reported.