Transient Growth Hormone Deficiency Research Articles

Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated, idiopathic GHD with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. The analysis included 260 patients (173 boys, 87 girls) with isolated, idiopathic GHD who had completed rhGH therapy and who had been reassessed for GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with the assessment of GH therapy effectiveness. The incidence of transient GHD, even with respect to pediatric criteria, was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in the patients with normal IGF-1 before treatment, suggesting that their diagnosis of GHD may have been a false positive. Further efforts should be made to avoid the overdiagnosis GHD and the overtreatment of patients.

Identification of a Novel IGSF1 Variant in Two Malaysian Male Siblings with Central Hypothyroidism and Macroorchidism.

IGSF1 mutation is the commonest cause of mild to moderate isolated central congenital hypothyroidism and has an X-linked recessive inheritance, primarily affecting males. Other notable clinical features are macroorchidism with delayed pubertal testosterone rise, large birth weight, increased body mass index, low prolactin, transient growth hormone deficiency and low prolactin. Two male siblings with central hypothyroidism were found to have a novel IGSF1 c.3467T>A variant that was likely pathogenic based on the family segregation study. The proband, aged 3 years presented at 18 days old with prolonged jaundice while his 16-year-old brother was only detected to have central hypothyroidism after the proband's genetic analysis result was known. Both siblings were obese, had large birth weights, macroorchidism and low prolactin. The proband's brother had intellectual disability while the proband had normal development. This case study highlights the importance of evaluation for the IGSF1 variant in patients with unexplained central hypothyroidism, especially when accompanied by X-linked inheritance and macroorchidism. Family segregation analysis allows detection of other affected family members or carriers who may also benefit from thyroxine treatment.

Is retesting in growth hormone deficient children really useful?

Patients with childhood-onset GH deficiency (GHD) are usually retested after achievement of near final height, to verify whether they need to continue GH treatment. We investigated if GH stimulation test is necessary to confirm a persistent status of GHD or if other parameters could be a reliable predictor of GHD persistence. One-hundred and sixty-four children with idiopathic GHD (55 females and 109 males) were retested when they reached near final height using GH releasing hormone (GHRH)+arginine test or arginine alone. At diagnosis, 23.8% of patients showed severe GHD (GH peak at diagnosis <5 ng/mL) and 76.2% showed partial GHD (GH peak <10 ng/mL). At time of retesting, 82.1% of severe GHD and 82.4% of partial GHD patients showed transient GHD. IGF-I levels were not different between persistent (0.18±1.18 SDS) and transient GHD subjects (0.17±0.82 SDS). Furthermore, among persistent severe GHD patients only two showed very reduced levels of IGF-I (<-2.0 SDS). The majority of patients idiopathic GHD proved to be transient. IGF-I levels alone do not discriminate subjects with persistent from those with transient GHD. Therefore, after the end of GH substitutive treatment, a re-evaluation of GH secretion is mandatory to verify the persistence of GHD in adulthood.

Delayed Adrenarche may be an Additional Feature of Immunoglobulin Super Family Member 1 Deficiency Syndrome.

Immunoglobulin super family member 1 (IGSF1) deficiency syndrome is characterized by central hypothyroidism, delayed surge in testosterone during puberty, macro-orchidism, and in some cases, hypoprolactinemia and/or transient growth hormone (GH) deficiency. Our patient was a 19-year-old male adolescent who had been treated since the age of 9 years with GH and thyroxine for an idiopathic combined GH, thyroid-stimulating hormone (TSH), and prolactin (PRL) deficiency. His GH deficiency proved to be transient, but deficiencies of TSH and PRL persisted, and he had developed macro-orchidism since the end of puberty. Brain magnetic resonance imaging and PROP1 and POU1F1 sequencing were normal. A disharmonious puberty (delayed genital and pubic hair development, bone maturation, and pubertal growth spurt, despite normal testicular growth) was observed as well as a delayed adrenarche, as reflected by very low dehydroepiandrosterone sulfate and delayed pubarche. Direct sequencing of the IGSF1 gene revealed a novel hemizygous mutation, c.3127T>C, p.Cys1043Arg. Pathogenicity of the mutation was demonstrated in vitro. Male children with an idiopathic combined GH, PRL, and TSH deficiency, showing persistent central hypothyroidism but transient GH deficiency upon retesting at adult height, should be screened for mutations in the IGSF1 gene, especially when macro-orchidism and/or hypoprolactinemia are present. We suspect that delayed adrenarche, as a consequence of PRL deficiency, might be part of the clinical phenotype of patients with IGSF1 deficiency.

IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management.

Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations. We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management. We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases. Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters. IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work-up, and long-term care.

Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence.

Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended.

Incidence and predictors of persistent growth hormone deficiency (GHD) in patients with isolated, childhood-onset GHD.

In a considerable proportion of patients with childhood-onset growth hormone (GH) deficiency (GHD), a normalisation of GH secretion at the attainment of final height (FH) is observed. The aim of the present study was to assess the incidence of, and to find out the predictors of, persistent and transient GHD, available in the pre-treatment period, in patients with childhood-onset isolated, non-acquired GHD. The analysis comprised 150 short children (117 boys), with childhood-onset isolated, non-acquired GHD who completed GH therapy and attained FH. Before treatment and at FH (in retesting), auxological parameters were measured, GH peak in stimulation tests and IGF-I concentration were assessed, and pituitary height (PHt) was measured before treatment. The incidence of persistent GHD was 12.0%. The patients with persistent GHD had before treatment significantly lower GH and IGF-I secretion, as well as significantly better increase of height SDS (DHSDS) during GH therapy than those with transient GHD. A negative correlation was observed between DHSDS and IGF-I concentration, but not between DHSDS and GH peak. There was no significant difference in the incidence of pituitary hypoplasia between the patients with persistent and transient GHD. The incidence of persistent GHD in patients with childhood-onset, isolated, non-acquired GHD is relatively low. Despite the fact that the predictors of persistent and transient GHD may be identified in childhood, a diagnosis of GHD should be verified in retesting after the attainment of FH in each case.

A middle aged woman with isolated ACTH deficiency associated with transient GH deficiency

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

The IGSF1 Deficiency Syndrome: Characteristics of Male and Female Patients

Ig superfamily member 1 (IGSF1) deficiency was recently discovered as a novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism. However, clinical and biochemical data regarding growth, puberty, and metabolic outcome, as well as features of female carriers, are scarce. Our objective was to investigate clinical and biochemical characteristics associated with IGSF1 deficiency in both sexes. All patients (n = 42, 24 males) from 10 families examined in the university clinics of Leiden, Amsterdam, Cambridge, and Milan were included in this case series. Detailed clinical data were collected with an identical protocol, and biochemical measurements were performed in a central laboratory. Male patients (age 0-87 years, 17 index cases and 7 from family studies) showed CeH (100%), hypoprolactinemia (n = 16, 67%), and transient partial GH deficiency (n = 3, 13%). Pubertal testosterone production was delayed, as were the growth spurt and pubic hair development. However, testicular growth started at a normal age and attained macro-orchid size in all evaluable adults. Body mass index, percent fat, and waist circumference tended to be elevated. The metabolic syndrome was present in 4 of 5 patients over 55 years of age. Heterozygous female carriers (age 32-80 years) showed CeH in 6 of 18 cases (33%), hypoprolactinemia in 2 (11%), and GH deficiency in none. As in men, body mass index, percent fat, and waist circumference were relatively high, and the metabolic syndrome was present in 3 cases. In male patients, the X-linked IGSF1 deficiency syndrome is characterized by CeH, hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight. A subset of female carriers also exhibits CeH.

Congenital disorders of glycosylation: other causes of ichthyosis

We read with interest the comprehensive review by Schmuth et al1 on inherited ichthyoses/generalized Mendelian disorders of cornification. We would like to point out that some congenital disorders of glycosylation (CDG) present ichthyosis. Associations have been described for MPDU1-CDG (formerly CDG-If), DOLK-CDG (CDG-Im), SRD5A3-CDG (CDG-Iq) and PIGL-CDG (CHIME syndrome, Zunich neuroectodermal syndrome). MPDU1-CDG is a defect in the N-glycan assembly in the endoplasmic reticulum (ER). The four reported patients showed skin involvement (ichthyosis and/or erythroderma). Other features included psychomotor retardation, seizures, hypotonia, gastrointestinal problems, visual impairment, dwarfism and transient growth hormone deficiency. The MPDU1 protein is considered to be a chaperone favoring the efficient utilization of dolicholphosphoglucose and dolicholphosphomannose in glycosylation. A reduced level of the glycosylphosphatidylinositol (GPI)-anchor CD59 has been found in these patients suggesting that they have also a deficiency in GPI-anchor biosynthesis (see PIGL-CDG).2, 3 DOLK-CDG is a defect in dolichol kinase, the last step of the dolichol phosphate biosynthesis. It shows a clinical spectrum with at one end a non-syndromic dilated cardiomyopathy (reported in nine patients),4 and at the other end a severe syndrome (reported in four patients) with ichthyosis, as well as dilated cardiomyopathy, epilepsy, microcephaly, visual impairment, hypoglycemia and death within the first 6 months.5 SRD5A3-CDG is a defect in polyprenol reductase, involved in the biosynthesis of dolichol. This cerebro-cerebello-oculo-cutaneous syndrome has been described in some 15 patients. Its skin component consists of ichthyosis, erythroderma and/or dry skin.6, 7 PIGL-CDG or CHIME syndrome is characterized by colobomas, congenital heart defects, early-onset migratory ichthyosiform dermatosis, mental retardation and ear anomalies, besides other clinical manifestations. This is a defect in an ER-localized enzyme that catalyzes the second step of GPI-anchor biosynthesis, the de-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol that occurs on the cytoplasmic side of the ER. It has been reported in eight patients.8

Hormonal and auxological data of the patients with persistent and transient GH deficiency, diagnosed according to different criteria after completion of growth-promoting therapy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Effect of growth hormone therapy on Taiwanese children with growth hormone deficiency

Human growth hormone (GH) has been successfully used in children with GH deficiency (GHD). However, there are few published data on the effect of GH in Taiwanese children with GHD. We performed a retrospective cohort study to identify factors influencing the effect of GH therapy on ethnic Chinese children with GHD in Taiwan. Idiopathic GHD can be classified into isolated GHD (IGHD) and multiple pituitary hormone deficiency (MPHD). The study looked at the effect of GH on the auxological, biochemical, and imaging parameters of 51 patients (13 girls and 38 boys) in three different diagnostic groups: MPHD (n = 12), IGHD (n = 8), and transient GHD (TGHD; n = 31). TGHD is defined as a GH peak >10 μg/L in re-evaluation by two GH stimulation tests approximately 6 months after discontinuation of GH therapy. The height velocity for first-year GH therapy was 7.61 ± 1.46, 8.14 ± 1.92, and 9.99 ± 2.75 cm/y in the TGHD, IGHD, and MPHD groups, respectively. After post hoc comparison, the MPHD group had a significantly accelerated height velocity in the first year compared to the TGHD group. Correlation analysis showed that a change in height standard deviation score (SDS) in the first year had a significant negative correlation with the following variables: peak GH (r = -0.52, p < 0.001), pretreatment height SDS (r = -0.49, p < 0.001), and height-target height (Ht-TH) SDS (r = -0.49, p < 0.001). Change in height SDS in the first 2 years had a significantly negative correlation with peak GH (r = -0.51, p < 0.001), insulin-like growth factor-1 SDS (r = -0.35, p = 0.022), height SDS (r = -0.60, p < 0.001), difference between bone age and chronological age (r = -0.46, p = 0.001), and Ht-TH SDS (r = -0.50, p = 0.001). After using multiple linear regression, the pretreatment GH peak value was found to be significantly associated with height increments after 1 year of GH treatment (B = -0.07, p = 0.014). The administration of GH to children with GHD results in a pronounced acceleration in linear growth during the first year of treatment, especially in those with MPHD. The diagnosis of GHD requires comprehensive auxological, biochemical, and brain magnetic resonance imaging assessment. We also suggest that patients with GHD, specifically IGHD, must undergo a re-evaluation of GH secretion after completion of GH therapy.

Effect van tekort en suppletie van groeihormoon en insuline-achtige groeifactor-I op hersenfuncties

Growth hormone (GH) and insulin-like growth factor 1 (IgF-1) are important for brain functioning. There are GH and IgF-1 receptors in numerous brain areas and cognitive impairments in patients with GH deficiency (GHD), Prader Willi syndrome (PWS), traumatic brain injury (TBI) and dementia seem related to low levels of these hormones. Also agerelated cognitive decline appears to be associated with reduced GH/IgF-1 levels. As GH substitution can alter hormone levels in the cerebral spinal fluid it may affect brain functioning. Indeed, a minimum duration of one year of GH substitution improved cognitive functioning of GHD patients. In Alzheimer patients the administration of a GH secretagogue substantially enhanced IgF-1 levels, but did not induce positive psychological effects. In contrast, one study on GH substitution in PWS patients indicated positive cognitive effects. As transient or permanent GHD frequently occurs in TBI patients, GH substitution may reduce brain impairment. The only study that investigated GH substitution in TBI patients indeed reported a beneficial effect of GH substitution on cognition, including memory. We conclude that GH substitution may reduce cognitive impairment or even improve brain functions in specific patient groups. Although GH substitution has been shown to improve cognitive functioning in various groups, effects are sometimes small and study groups are frequently heterogeneous with a small sample size. As the available evidence of the cognitive effects of GH substitution is limited, more studies are needed to demonstrate that GH substitution may induce cognitive improvement in distinctive patient groups with GHD.

Diagnosis of growth hormone (GH) deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency

BackgroundMost patients with childhood non-organic growth hormone (GH) deficiency (GHD) produce a normal GH peak as young adults. Our objectives were to better define this transient GHD and evaluate the factors influencing the growth response of patients with pituitary stalk interruption syndrome (PSIS).MethodsWe studied 72 prepubertal patients with a GH peak < 6.7 ng/ml after 2 stimulation tests, treated with 0.2 mg GH/kg/w for at least 3 years. Group 1 (n = 53, 4.7 ± 4.0 years) had PSIS and Group 2 (n = 19, 9.2 ± 3.0 years) had transient GHD and normal pituitary.ResultsAt diagnosis, 64% of Group 1 and one Group 2 were < 5 years old. The growth rate of 59% Group 1 and two Group 2 patients was ≤ -2 SDS. The GH peak of 64% Group 1 patients and no Group 2 patients was < 3 ng/ml. The plasma insulin-like growth factor-1 of all Group 1 and all but one Group 2 patients was ≤ -2 z scores.During the first year of GH treatment, the growth rate was ≥ 2 SDS in 81% Group 1 and 37% Group 2 patients. In Group 1, it was negatively correlated with the GH peak before treatment (P < 0.03), and with the difference between the target and adult heights (P < 0.01).The height gain SDSs between diagnosis and adult height were 1.7 ± 1.2 in Group 1 (n = 30) and 1.08 ± 0.8 in Group 2 (n = 12, P = 0.05).ConclusionThe factors of the growth response to GH treatment should be analysed separately for each population: with and without PSIS or other markers.

Evaluation of Permanent Growth Hormone Deficiency (GHD) in Young Adults with Childhood Onset GHD: A multicenter study

Background: Reconfirming the diagnosis of childhood onset growth hormone deficiency (GHD) in young adults is necessary to demonstrate the need for continuation of GH therapy.Objective: This nationally−based study was planned to establish GH status during adulthood in childhood−onset GH deficient patients and to evaluate factors that would predict persistency of the GHD.Methods: In this multicenter study, 70 GH deficient patients who had reached final height were evaluated after completion of GH treatment. Fifty−two patients (74%) had isolated GHD and 18 patients (26%) had multiple pituitary hormone deficiency (MPHD). Patients who had reached final height and the pubertal Tanner stage 5 were reevaluated for GH status. After at least 6 weeks of cessation of GH treatment, patients were retested with insulin induced hypoglycemia.Results: GHD was found to be transient in 64.3% of all patients. Of the isolated GH deficient patients 82.7% had transient GHD, whereas 88.9% of the MPHD patients showed persistent GHD. Comparison of isolated GH deficient and multiple hormone deficient patients indicated higher peak GH, IGF−I and IGFBP−3 levels in isolated GH deficient patients. No parameter was significantly different in the transiently and persistently GH deficient patients with respect to gender. Although specificity of IGF−I value of less than −2 SD showing persistency of GHD was lower than the specificity of IGFBP−3 value of less than −2 SD (65.7% vs 84%), negative predictive values were similar for the two parameters (85.2% and 84%, respectively).Conclusion: Most of the cases of childhood onset GHD are idiopathic and the GHD is transient. In patients with MPHD, GHD is generally permanent. Low IGF−I and IGFBP−3 levels are supporting findings to show persistency of the GHD.Conflict of interest:None declared.

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to FLNB mutations

Spondylocarpotarsal synostosis: Long‐term follow‐up of a case due to <i>FLNB</i> mutations

A Boy with "transient" Growth Hormone Deficiency in Prepubertal Stage Despite Normal Growth Hormone Secretion in Childhood and after Puberty

Transient growth hormone deficiency (GHD) is occasionally found in prepubertal individuals, and this phenomenon has been variously interpreted. Sex steroids enhance GH secretion; however, the cut-off values of provocative GH tests are not modified according to the physiological changes. Physiological changes in sex steroid levels are thought to cause the image of transient GHD. In addition, the reproducibility of provocative GH tests makes the interpretation complicated. We experienced a case of a boy with short stature who had undergone provocative GH tests at three different times: childhood (5 and 7 years old), before puberty (12 years old), and in adolescence (15 years old). Although the responses of GH in his childhood and adolescence were within the normal range, his prepubertal GH response was extremely low, as if he had "complete" GHD (peak GH: insulin test, 0.60 ng/ml; clonidine test, 0.78 ng/ml). No morphological changes were observed in the pituitary gland or hypothalamus on MRI. The level of insulin-like growth factor 1 was in the normal range for his age at this time. Here, we report the clinical course and endocrinological data of this case, and suggest that transient GHD is caused not only by the physiological effects of sex steroids but also by certain mechanisms that actively reduce GH secretion.

Growth and Adult Height in Atypical Coeliac Patients, With or Without Growth Hormone Deficiency

To evaluate the effect of a gluten-free diet on growth and adult height, when available, in coeliac children without gastrointestinal symptoms. Sixty-one coeliac children without gastro-intestinal symptoms were included in the study. The age at diagnosis was 9.50 +/- 3.3 years. Thirty-eight had short stature at diagnosis (< 10th percentile) and 23 had normal stature. Thirty-seven reached adult height. After beginning the diet an increase in growth velocity was seen in 30 patients (responders) (20 with initial short stature), while in 31 patients (18 with short stature) there was no catch-up growth (non-responders). Bone age at diagnosis was significantly more delayed in the responders than in the non-responders. Target height was significantly higher in children with normal stature at diagnosis than those with short stature. Growth hormone (GH) deficiency was found and confirmed after 6-12 months of diet in 12 of the 38 patients (32%) with short stature. In the group of the 30 'short' patients who attained final height, target height was attained or improved in 12 patients (40%): in eight of the 16 (50%) responders and in four of the 14 (29%) non-responders; in eight (all responders) out of 22 (36%) without GH deficiency, and in four out of eight (50%) patients with GH deficiency treated with GH (all non-responders). In children in whom coeliac disease is diagnosed because of short stature, a gluten-free diet will be successful if at diagnosis there is a delay of bone age and in the first year of diet there is an evident catch-up growth. When this does not occur, i.e. in half of the patients (18 out of 38), it may be because of an associated and transient GH deficiency. In these patients a period of GH replacement therapy as well as a gluten-free diet may improve their final height.

Growth Hormone (GH) Secretion in Patients with Childhood-Onset GH Deficiency: Retesting after One Year of Therapy and at Final Height

Background: Recent studies have shown that many patients treated with growth hormone (GH) during childhood because of idiopathic GH deficiency (GHD) are no longer GH deficient when retested after cessation of GH therapy when final height is achieved. These patients are labelled as transient GHD. We hypothesized that normalization of GH secretion in transient GHD could occur earlier during the course of GH treatment, which could allow earlier cessation of GH treatment. Methods: In a retrospective study, GH secretion was re-evaluated after cessation of GH treatment at final height in 43 patients diagnosed during childhood as idiopathic GHD (10 with multiple pituitary hormonal deficiencies (MPHD) and 33 with isolated GHD (IsGHD)). In a prospective study, GH secretion was re-assessed after interruption of GH treatment given for 1 year in 18 children with idiopathic GHD (2 MPHD, 16 IsGHD). GH secretion was evaluated by glucagon or insulin stimulation tests. Results: In the retrospective study, all the 10 patients with MPHD and 64% of the 33 patients with IsGHD were still deficient at re-evaluation using the paediatric criteria to define GHD (GH peak <10 ng/ml at provocative test). The proportion of persisting deficiency was greater in patients with complete IsGHD (86%, 12/14 patients) than in patients with partial IsGHD (47%, 9/19 patients). With the criteria proposed in adulthood (GH peak <3 ng/ml), all the 10 patients with MPHD were still considered to be deficient. In contrast, only 15% (5/33 patients) with IsGHD had a maximal GH value <3 ng/ml (36% of the 14 patients with complete IsGHD and none of the 19 patients with partial IsGHD). In the prospective study, after interruption of GH therapy given for 1 year, the 2 patients with MPHD were still GHD at re-evaluation and they resumed GH treatment. Among the 16 patients with IsGHD, 13 (81%) were still deficient (peak response <10 ng/ml) after 1 year. Two of the 3 patients in whom GHD was not confirmed at retesting after 1 year GH showed again a deficient response at second retesting. Conclusions: Although many patients diagnosed with IsGHD during childhood have a normalized GH secretory capacity when retested during adulthood, early retesting after interruption of GH treatment given for 1 year during childhood does not enable to determine if GH therapy has to be discontinued before cessation of growth.

Effect of Short-Term Testosterone Treatment on Leptin Concentrations in Boys with Pubertal Delay

Testosterone administration increases growth hormone (GH) secretion and decreases the plasma leptin concentration in men. We evaluated the effect of increased GH secretion due to short-term testosterone treatment on leptin concentrations. Ten boys aged 14.8 ± 0.2 (mean ± SE) years with transient GH deficiency caused by pubertal delay were evaluated before and after (3 months) 4 intramuscular injections of 100 mg testosterone heptylate, given at 15-day intervals. The leptin concentration decreased from 5.4 ± 1.3 to 3.6 ± 1.1 μg/l (p < 0.001), despite a weight gain of 3.4 ± 0.5 kg. There were significant increases in body mass index (BMI), from –0.2 ± 0.5 to 0.2 ± 0.5 SD, p < 0.005, in GH peak after stimulation test, from 6.3 ± 0.5 to 21.7 ± 2.9 μg/l, p < 0.0003, in plasma testosterone, from 0.6 ± 0.1 to 6.5 ± 1.3 μg/l, p < 0.001, in insulin-like growth factor-I (IGF-I), from 152 ± 21 to 330 ± 30 μg/l, p < 0.0001, and in IGF-binding protein-3 (IGFBP-3), from 4.2 ± 0.5 to 5.4 ± 0.4 mg/l, p < 0.01. But there were no changes in blood glucose (4.7 ± 0.1 and 4.8 ± 0.1 mmol/l), or plasma fasting insulin (9.0 ± 1.2 and 8.1 ± 1.3 mIU/l). The leptin concentrations were positively correlated with the BMI before (p < 0.03) and after (p < 0.04) testosterone, but not with the GH peak after stimulation, or with plasma testosterone, IGF-I or IGFBP-3. The leptin and insulin concentrations after testosterone treatment were positively correlated (p < 0.04). Thus, short-term testosterone treatment of boys with pubertal delay decreases their leptin concentrations. The lack of correlation with GH secretion or with its changes, despite the dramatic increase in GH secretion, and the lack of change in insulin are additional features suggesting that testosterone increases the leptin concentration mainly by an effect on adipose tissue.