ABNORMAL THYROXINE METABOLISM IN HYPOSOMATOTROPHIC DWARFISM AND INHIBITION OF RESPONSIVENESS TO TRH DURING GH THERAPY

Thyrotropin (TSH) release and thyroxine metabolism have been studied in order to determine whether human growth hormone (GH) administration is causally related to the occasional development of secondary hypothyroidism in GH-deficient dwarfs. Five hyposomatotrophic dwarfs and one normal child were studied. The TSH response to synthetic thyrotropin-releasing hormone (TRH) was normal in all, regardless of thyroid functional status. Before GH administration, two of the three clinically euthyroid dwarfs were found to have daily thyroxine degradation rates in the hypothyroid range although serum total and free thyroxine levels were normal. Following six to ten days of GH treatment, TSH levels fell slightly and the TSH response to TRH was blunted. During long-term GH treatment of four dwarfs no significant change in thyroid function was observed. In addition, TSH responsiveness to TRH recovered in three of these four chronically treated patients, including one who was frankly hypothyroid. The growth rate of the three clinically euthyroid dwarfs improved during long-term GH therapy; nevertheless, the addition of 50µg triiodothyronine to the treatment regimen of the dwarf in whom the thyroxine degradation rate was lowest resulted in a markedly improved growth rate. These studies indicate that a state of hypothyroidism that is undetectable by measurement of total serum thyroxine and free thyroxine exists in some GH-deficient patients. GH may be necessary for normal thryoxine metabolism and action. Such a GH effect might explain the observed influence of GH on TSH release. On the other hand, the demonstrated abnormality in thyroxine metabolism may result from mild, preexisting TSH deficiency.

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Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature

International Journal of Endocrinology ◽

10.1155/2019/8454303 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Jung-Eun Moon ◽

Cheol Woo Ko

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Gestational Age ◽

Small For Gestational Age ◽

Human Growth ◽

Bone Age ◽

Pediatric Endocrinology ◽

Gh Therapy ◽

Gh Treatment ◽

The Impact

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective. To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital. Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.

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Dynamics of bone turnover in children with GH deficiency treated with GH until final height

Acta Endocrinologica ◽

10.1530/eje.0.1420549 ◽

2000 ◽

pp. 549-556 ◽

Cited By ~ 25

Author(s):

GI Baroncelli ◽

S Bertelloni ◽

C Ceccarelli ◽

D Cupelli ◽

G Saggese

Keyword(s):

Growth Rate ◽

Bone Turnover ◽

Final Height ◽

Term Treatment ◽

Bone Marker ◽

First Year ◽

Type I ◽

Gh Treatment ◽

Long Term Treatment

OBJECTIVE: To examine the dynamics of bone turnover in children with growth hormone deficiency (GHD) during long-term treatment. DESIGN: We longitudinally measured growth velocity and serum concentrations of osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in 24 patients with GHD during long-term GH treatment until final height (age: 7.7+/-0.7 and 16.9+/-0.5 years at baseline and at final height respectively). RESULTS: At baseline, OC, PICP, and ICTP levels were significantly (P<0.0001) reduced in comparison with prepubertal bone age-matched controls (10.2+/-2.3 microgram/l and 22.5+/-7.6 microgram/l; 187.8+/-26.2 microgram/l and 328. 4+/-74.3 microgram/l; 7.7+/-2.0 microgram/l and 14.2+/-1.3 microgram/l respectively). During the first year of treatment mean levels of the bone markers increased significantly (P<0.0001) with a peak at 12 months. After the first year of treatment, OC and PICP levels progressively declined, whereas ICTP levels remained stable until the final height; in any case, bone marker levels remained significantly higher (P<0.03-P<0.0001) than baseline. The change in bone marker levels at 6 and 12 months of treatment with respect to the baseline values was not related to growth rate during long-term treatment or final height. CONCLUSIONS: The results show that children with GHD have reduced bone turnover at baseline, and that long-term GH treatment is associated with a stimulation of bone turnover. OC, PICP, and ICTP do not predict growth rate during long-term treatment or final height in children with GHD.

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Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

Acta Endocrinologica ◽

10.1530/eje.0.1470625 ◽

2002 ◽

pp. 625-633 ◽

Cited By ~ 40

Author(s):

MB Ranke ◽

CJ Partsch ◽

A Lindberg ◽

HG Dorr ◽

M Bettendorf ◽

...

Keyword(s):

Turner Syndrome ◽

Adult Height ◽

Bone Age ◽

First Year ◽

Gh Therapy ◽

Gh Treatment ◽

Height Gain ◽

Puberty Onset

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

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Growth Hormone Therapy and Respiratory Disorders: Long-Term Follow-up in PWS Children

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-1831 ◽

2013 ◽

Vol 98 (9) ◽

pp. E1516-E1523 ◽

Cited By ~ 28

Author(s):

Jenny Berini ◽

Valeria Spica Russotto ◽

Paolo Castelnuovo ◽

Stefania Di Candia ◽

Luigi Gargantini ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Central Apnea ◽

Respiratory Disturbance Index ◽

Gh Therapy ◽

Gh Treatment ◽

Adenotonsillar Hypertrophy ◽

Disturbance Index ◽

Obstructive Sleep ◽

Respiratory Disturbance

Context: Adenotonsillar tissue hypertrophy and obstructive sleep apnea have been reported during short-term GH treatment in children with Prader-Willi syndrome (PWS). Objective: We conducted an observational study to evaluate the effects of long-term GH therapy on sleep-disordered breathing and adenotonsillar hypertrophy in children with PWS. Design: This was a longitudinal observational study. Patients and Methods: We evaluated 75 children with genetically confirmed PWS, of whom 50 fulfilled the criteria and were admitted to our study. The patients were evaluated before treatment (t0), after 6 weeks (t1), after 6 months (t2), after 12 months (t3), and yearly (t4–t6) thereafter, for up to 4 years of GH therapy. The central apnea index, obstructive apnea hypopnea index (OAHI), respiratory disturbance index, and minimal blood oxygen saturation were evaluated overnight using polysomnography. We evaluated the adenotonsillar size using a flexible fiberoptic endoscope. Results: The percentage of patients with an OAHI of >1 increased from 3 to 22, 36, and 38 at t1, t4, and t6, respectively (χ2 = 12.2; P < .05). We observed a decrease in the respiratory disturbance index from 1.4 (t0) to 0.8 (t3) (P < .05) and the central apnea index from 1.2 (t0) to 0.1 (t4) (P < .0001). We had to temporarily suspend treatment for 3 patients at t1, t4, and t5 because of severe obstructive sleep apnea. The percentage of patients with severe adenotonsillar hypertrophy was significantly higher at t4 and t5 than at t0. The OAHI directly correlated with the adenoid size (adjusted for age) (P < .01) but not with the tonsil size and IGF-1 levels. Conclusion: Long-term GH treatment in patients with PWS is safe; however, we recommend annual polysomnography and adenotonsillar evaluation.

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Long-term Echocardiographic and Cardioscintigraphic Effects of Growth Hormone Treatment in Adults With Prader-Willi Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1063 ◽

2015 ◽

Vol 100 (5) ◽

pp. 2106-2114 ◽

Cited By ~ 7

Author(s):

Paolo Marzullo ◽

Claudio Marcassa ◽

Alessandro Minocci ◽

Riccardo Campini ◽

Ermanno Eleuteri ◽

...

Keyword(s):

Left Ventricle ◽

Ejection Fraction ◽

Body Mass ◽

Radionuclide Angiography ◽

Left Ventricle Ejection Fraction ◽

Prader Willi Syndrome ◽

Gh Therapy ◽

Gh Treatment ◽

Study Participants

Abstract Context: In Prader-Willi syndrome (PWS), an altered GH secretion has been related to reduced cardiac mass and systolic function compared to controls. Objective: The objective was to evaluate the cardiovascular response to a 4-year GH therapy in adult PWS patients. Study Participants: Study participants were nine severely obese PWS adults (three females, six males) and 13 age-, gender-, and body mass index-matched obese controls. Methods: In an open-label prospective study, assessment of endocrine parameters and metabolic outcome, whole-body and abdominal fat scans, echocardiography, and radionuclide angiography in unstimulated and dobutamine-stimulated conditions were conducted at baseline and after 1 and 4 years of GH treatment. Results: GH treatment increased IGF-1 (P < .0001), decreased C-reactive protein levels (P < .05), improved visceral fat mass (P < .05), and achieved near-significant changes of fat and fat-free body mass in PWS patients. Left ventricle mass indexed by fat mass increased significantly after 1 and 4 years of GH therapy (P < .05) without evident abnormalities of diastolic function, while a trend toward a reduction of the ejection fraction was documented by echocardiography (P = .054). Radionuclide angiography revealed stable values throughout the study of both the left and right ventricle ejection fractions, although this was accompanied by a statistically nonsignificant reduction of the left ventricle filling rate. A positive association between lean body mass and left ventricle ejection fraction was evident during the study (P < .05). Conclusions: GH therapy increased the cardiac mass of PWS adults without causing overt abnormalities of systolic and diastolic function. Although the association between lean mass and left ventricle ejection fraction during GH therapy corroborates a favorable systemic outcome of long-term GH treatment in adults with PWS, subtle longitudinal modifications of functional parameters advocate appropriate cardiac monitoring in the long-term therapeutic strategy for PWS.

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SULPHATION FACTOR ACTIVITY AND GROWTH RATE DURING LONG-TERM TREATMENT OF PATIENTS WITH PITUITARY DWARFISM WITH HUMAN GROWTH HORMONE

Acta Endocrinologica ◽

10.1530/acta.0.0690417 ◽

1972 ◽

Vol 69 (3) ◽

pp. 417-433 ◽

Cited By ~ 36

Author(s):

Kerstin Hall ◽

Patrick Olin

Keyword(s):

Growth Hormone ◽

Growth Rate ◽

Human Growth Hormone ◽

Human Growth ◽

Term Treatment ◽

Factor Activity ◽

Duration Of Treatment ◽

Pituitary Dwarfism ◽

Long Term Treatment

ABSTRACT Twenty patients with pituitary dwarfism were treated for nine months to 2½ years with human growth hormone (HGH) prepared according to Roos et al. (1963). Eleven of them had previously been given other HGH preparations for one to five years. During the first two years of treatment with HGH in a dose of 0.2 mg (0.4 IU) and 0.3 mg (0.6 IU) per kg body weight per week, the increase in growth rate was two- to threefold, and three- to fivefold, respectively. Long-termed treatment with HGH was accompanied by a decreasing ability of the hormone to stimulate growth. Cortisone acetate, in replacement doses, had no influence on this growth rate. During the present study only one of the 20 patients developed antibodies to HGH. The levels of sulphation factor (SF) activity in serum were low before treatment and increased significantly during treatment with HGH. There was a linear relationship between the SF activity in the serum and the slope of the growth carves. Both increased with the dose of HGH administered but decreased with duration of treatment.

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IGF-I therapy in growth disorders

Acta Endocrinologica ◽

10.1530/eje-07-0187 ◽

2007 ◽

Vol 157 (suppl_1) ◽

pp. S57-S60 ◽

Cited By ~ 11

Author(s):

Ron G Rosenfeld

Keyword(s):

Clinical Trials ◽

Growth Disorders ◽

Controlled Clinical Trials ◽

Gh Therapy ◽

Gh Treatment ◽

Gh Receptor ◽

Potential Efficacy ◽

Igf I ◽

Short And Long Term

Patients with GH insensitivity, typically resulting from mutations affecting the GH receptor (GHR), GHR signaling cascade, or the IGF-I gene, are, generally, unresponsive to GH therapy. Beginning in the 1990s, clinical trials of IGF-I administration in such patients demonstrated both short- and long-term efficacy, although not to the degree observed with GH treatment of naïve GH-deficient patients. Adverse effects, including hypoglycemia, lymphoid overgrowth, benign intracranial pressure, and coarsening of facial features, have been observed, but, in general, have proven to be transient. As interest in the potential efficacy of IGF-I treatment for children currently labeled as idiopathic short stature increases, it will be important to have controlled clinical trials of GH, versus IGF-I versus combination, GH + IGF-I.

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Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome

Acta Endocrinologica ◽

10.1530/eje.1.01988 ◽

2005 ◽

Vol 153 (4) ◽

pp. 499-502 ◽

Cited By ~ 12

Author(s):

P Cabanas ◽

T García-Caballero ◽

J Barreiro ◽

L Castro-Feijóo ◽

R Gallego ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Turner Syndrome ◽

Carcinoma Cells ◽

Receptor Expression ◽

Papillary Thyroid ◽

Long Term Effects ◽

Gh Therapy ◽

Gh Treatment

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH–IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

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Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11

Acta Endocrinologica ◽

10.1530/eje-08-0413 ◽

2008 ◽

Vol 159 (3) ◽

pp. 203-208 ◽

Cited By ~ 43

Author(s):

C Noordam ◽

P G M Peer ◽

I Francois ◽

J De Schepper ◽

I van den Burgt ◽

...

Keyword(s):

Protein Tyrosine Phosphatase ◽

Noonan Syndrome ◽

Adult Height ◽

Final Height ◽

Tyrosine Phosphatase ◽

Receptor Type ◽

Gh Therapy ◽

Gh Treatment ◽

Protein Tyrosine

ContextNoonan syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. Short-term effect of GH therapy in NS is beneficial, reports on the effect on adult height are scarce.ObjectiveTo determine the effect of long-term GH therapy in children with NS.DesignTwenty-nine children with NS were treated with GH until final height was reached.SettingHospital endocrinology departments.PatientsChildren with the clinical diagnosis of NS, with mean age at the start of therapy of 11.0 years, 22 out of 27 tested children had a mutation in the protein tyrosine phosphatase, non-receptor-type 11 gene (PTPN11 gene).InterventionsGH was administered subcutaneously at 0.05 mg/kg per day until growth velocity was 1 cm/6 months.Main outcome measureLinear growth (height) was measured at 3-month intervals in the first year and at 6-month intervals thereafter until final height.ResultsAt the start of treatment, median height SDS (H-SDS) was −2.8 (−4.1 to −1.8) and 0.0 (−1.4 to +1.2), based on national and Noonan standards respectively. GH therapy lasted for 3.0–10.3 years (median, 6.4), producing mean gains in H-SDS of +1.3 (+0.2 to +2.7) and +1.3 (−0.6 to +2.4), based on national and Noonan standards respectively. In 22 children with a mutation in PTPN11 mean gain in H-SDS for National standards was +1.3, not different from the mean gain in the five children without a mutation in PTPN11+1.3 (P=0.98).ConclusionLong-term GH treatment in NS leads to attainment of adult height within the normal range in most patients.

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Long-term results of GH therapy in GH-deficient children treated before 1 year of age

Acta Endocrinologica ◽

10.1530/eje.0.1400029 ◽

1999 ◽

pp. 29-34 ◽

Cited By ~ 23

Author(s):

F Huet ◽

JC Carel ◽

JL Nivelon ◽

JL Chaussain

Keyword(s):

Clinical Presentation ◽

Gh Deficiency ◽

Growth Parameters ◽

Long Term Results ◽

Long Term Effects ◽

Target Height ◽

Gh Therapy ◽

Gh Treatment ◽

Catch Up

OBJECTIVES: To evaluate the long-term effects of GH therapy in early diagnosed GH-deficient patients treated before 1 year of age. Study design: We studied all 59 patients (33 males) recorded by Association France-Hypophyse and treated with GH (0.50+/-0.15 IU/kg (S.D.) per week) before 1 year of age. Clinical presentation and growth parameters under GH treatment were analyzed. RESULTS: Neonatal manifestations of hypopituitarism were frequent: hypoglycemia (n=50), jaundice (n=25) and micropenis (n=17/33). Although birth length was moderately reduced (-0.9+/-1.4), growth retardation at diagnosis (5.8+/-3.8 months) was severe (-3.5+/-1.9 standard deviation scores (SDS)). Fifty patients (85%) had thyrotropin and/or corticotropin deficiency. After a mean duration of GH therapy of 8.0+/-3.6 years, change in height SDS was +3.11+/-2.06 S.D., exceeding 4 SDS in 19 patients. Only 9 patients (15%) did not reach a height of -2 S.D. for chronological age and 20 patients (34%) exceeded their target height. Pretreatment height SDS was independently associated with total catch-up growth. CONCLUSION: Conventional doses of GH allow normalization of height in patients with early GH deficiency and treatment.

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