16例伴生长激素缺乏的多种垂体激素缺乏患者的临床特点及生长激素治疗效果分析

目的探讨伴生长激素缺乏(GHD)的多种垂体激素缺乏症(MPHD)患者的临床特点以及生长激素(GH)治疗效果。方法回顾性分析16例伴有生长激素缺乏的多种垂体激素缺乏患者的临床资料。结果本研究纳入了16例MPHD的患者,其中伴甲状腺功能减退症9例、伴低促性腺激素性性腺功能低减13例和伴肾上腺皮质功能减退6例。臀位、足先露和难产等不良生产史患者10例。骨龄(11.0±3.5)岁,明显落后实际年龄。L-Dopa-GH激发试验GH峰值为(0.14±0.17)ng/m L,GH治疗平均剂量(0.11±0.02)IU/kg。治疗后IGF-1水平及生长速度均明显增加。结论排除下丘脑、垂体占位等病变后,伴GH缺乏的MPHD患者在纠正其他轴系激素缺乏后,使用GH治疗可明显改善身高,并且无严重不良事件发生。     

The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency

In a double-blind, placebo-controlled trial, we studied the effects of six months of growth hormone replacement in 24 adults with growth hormone deficiency. Most of the patients had acquired growth hormone deficiency during adulthood as a consequence of treatment for pituitary tumors, and all were receiving appropriate thyroid, adrenal, and gonadal hormone replacement. The daily dose of recombinant human growth hormone (rhGH) was 0.07 U per kilogram of body weight, given subcutaneously at bedtime. The mean (+/- SE) plasma concentration of insulin-like growth factor I increased from 0.41 +/- 0.05 to 1.53 +/- 0.16 U per liter during rhGH treatment. Treatment with rhGH had no effect on body weight. The mean lean body mass, however, increased by 5.5 +/- 1.1 kg (P less than 0.0001), and the fat mass decreased by 5.7 +/- 0.9 kg (P less than 0.0001) in the group treated with growth hormone; neither changed significantly in the placebo group. The basal metabolic rate, measured at base line and after one and six months of rhGH administration, increased significantly; the respective values were 32.4 +/- 1.4, 37.2 +/- 2.2, and 34.4 +/- 1.6 kcal per kilogram of lean body mass per day (P less than 0.001 for both comparisons). Fasting plasma cholesterol levels were lower (P less than 0.05) in the rhGH-treated group than in the placebo group, whereas plasma triglyceride values were similar in the two groups throughout the study. We conclude that growth hormone has a role in the regulation of body composition in adults, probably through its anabolic and lipolytic actions.     

A case of pycnodysostosis with growth hormone deficiency

Pycnodysostosis is a skeletal dysplasia characterized by short stature. Treatment of pycnodysostosis with growth hormone (GH) has not been reported so far. We describe a case of pycnodysostosis with growth hormone deficiency in addition to low mean insulin-lüce growth factor 1 (IGF-1) concentration. Complete GH deficiency was determined by two pharmacological provocative tests (insulin and L-dopa). A good height-velocity response was obtained after GH replacement treatment. Pycnodysostosis with GH deficiency and replacement therapy have not been reported previously, to the best of our knowledge.     

Familial growth hormone deficiency associated with MRI abnormalities

Idiopathic growth hormone deficiency is, in most cases, a sporadic condition. In a number of these patients magnetic resonance imaging (MRI) demonstrates a small anterior pituitary, small or absent pituitary stalk, and ectopically located posterior pituitary. These findings have been attributed to a developmental defect, trauma, or ischemia at birth. We report on a case of familial isolated growth hormone deficiency with mother and son demonstrating the MRI findings described above. The son also had a Chiari type I malformation and medial deviation of the carotid arteries secondary to a narrow skull base. Testing failed to identify a mutation in either the Pit-1 gene or GH gene cluster. This case appears to be an autosomal dominant defect in early development, lending support to the hypothesis that dysgenesis, rather than birth trauma, may cause a small anterior pituitary and ectopic posterior pituitary. Am. J. Med. Genet. 80:128–132, 1998. © 1998 Wiley-Liss, Inc.     

Poland''s syndrome associated with growth hormone deficiency.

A 9 year old boy with Poland's syndrome (absence of the left pectoralis major muscle associated with an ipsilateral malformation of the hand) and isolated growth hormone deficiency, owing to anatomical abnormalities of the pituitary gland, is described. MRI brain scan showed severe hypoplasia of both the sella and anterior lobe of the pituitary gland with absence of the pituitary stalk and ectopia of the posterior lobe. Association of Poland's syndrome and growth hormone deficiency has not been described previously.     

Growth hormone deficiency and growth hormone therapy in Ullrich-Turner-Syndrome

Summary In a girl with Ullrich-Turner-Syndrome (gonadal dysgenesis 45, XO) and growth hormone deficiency, 10 U of human growth hormone/m² body surface area/week increased the growth rate from 2.0 to 4.1 cm/year. Doses of up to 36 U/m²/week did not improve the growth rate in 4 girls with Ullrich-Turner-Syndrome who had normal plasma growth hormone concentration and incretion. We conclude that growth hormone therapy is unsuccessful in dwarfism in Ullrich-Turner-Syndrome and should be reserved for patients with proven growth hormone deficiency.Supported by Deutsche Forschungsgemeinschaft, SFB 51/C10     

Immunological studies in patients with isolated growth hormone deficiency.

The proportion of total T cells, OKT4+ (helper/inducer phenotype) T cells and activated T cells (Tac+) in four growth hormone deficient children were compared to simultaneously studied age and sex matched healthy controls. Proportions of OKT8+ T cells (suppressor/cytotoxic phenotype), and B lymphocytes (surface immunoglobulin positive) were increased when compared to healthy controls. Increased proportion of OKT8+ T cells resulted in abnormally low ratios of OKT4+/OKT8+ cells. Proliferative response to PHA and in the AMLR were comparable to the control group. In allogeneic MLR, T cells from three of four patients responded poorly and three of four patients non-T cells stimulated poorly in MLR. Con A activated suppressor cell activity was comparable to healthy control group. This study supports the role of growth hormone in certain immune response.     

A case of Goldenhar syndrome associated with growth hormone deficiency

Summary We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency.     

Regulation by catecholamines of spontaneous growth hormone secretion in the baboon

To gain an increased understanding of the role of central neurotransmitters in the regulation of spontaneous growth hormone (GH) secretion in the primate, we investigated the effects of peripheral intravenous infusion of the alpha-adrenergic receptor-blocking agent, phentolamine (5.0-mg bolus and 1.5 mg . kg-1 . 12 h-1), and the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (MPT, 300 mg . kg-1 . 24 h-1), on the pattern of GH secretion in five adolescent male baboons. Serum GH concentrations were measured in blood samples taken at 20-min intervals over 12 h (0530-1730) after an overnight fast. In nontreatment control studies, GH secretion exhibited a predictable rhythmic oscillation with a mean period of 5.7 +/- 0.4 (SE) h. Phentolamine significantly decreased the 12-h mean and integrated GH concentrations compared to control values, but the small peaks of GH, which could be distinguished from base-line concentrations in three of the animals, occurred at the same time as during control studies. Whereas alpha-methyl-p-tyrosine slightly reduced serum levels of GH, it significantly increased the GH pulse frequency in the baboons. A two- to fourfold increase in serum prolactin levels occurred in all animals treated with MPT. These findings suggest that alpha-adrenergic pathways play a stimulatory role in maintaining spontaneous daytime GH secretion in the baboon and that one or more catecholamines are involved in the generation of rhythmic GH release.     

Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

Abstract

Background: Ataxia telangiectasia (A-T) is a devastating human recessive disorder characterised by progressive cerebellar ataxia, immunodeficiency, genetic instability, and cancer susceptibility. In addition, many patients suffer from growth failure. Methods: We analyzed growth and IGF-1/BP3 levels of 24 A-T-patients compared with an age-matched group of healthy controls (n?=?36). Results: Ten (41.7%) A-T patients and none of healthy controls had an IGF-1 level below the 3rd percentile for age. The growth hormone (GH) stimulation tests revealed a severe GH deficiency with no increase of >5?ng/ml in six of the ten A-T patients. The IGF-1 generation tests revealed normal increases in IGF-1 values in all patients. Conclusion: Our results show that a disturbance in the GH/IGF-1 axis was present in 58.3% of A-T patients. Low levels of GH were the result of reduced central GH secretion. GH treatment may be a therapeutic option for A-T patients with severe growth failure.     

Ultrasonic evaluation of endometrial growth in women with normal cycles during spontaneous and stimulated cycles

Ultrasound scanning of the endometrium was performed through the menstrual cycle in normal, ovulating women in 20 unstimulated cycles (A), 13 clomiphene citrate (CC)/human menopausal gonadotrophin (HMG)/human chorionic gonadotrophin (HCG)-stimulated cycles (B) and 20 CC/HMG/HCG-stimulated cycles with oocyte collection (C). A total of 294 endometrial scans were performed and the texture and thickness of the endometrium registered. All data were related to the day of the luteinizing hormone (LH) peak or to HCG administration (day 0). There was no difference between groups in the image of the endometrium, which consisted of thin echogenic lines from day -10 until day 0 (99%). Three thin echogenic lines were seen in the pre-ovulatory endometrium in all cycles. During the luteal phase, confluent, thick echogenic lines were observed in all but two cycles, where the pre-ovulatory pattern persisted. The endometrium reached a mean thickness at days -1 to +1 of 6.4 mm in group A and 6.1 mm in groups B and C together. The endometrium was thinner at days -7 to -5 and -4 to -2 in groups B and C together (2.7 mm and 4.2 mm) compared with group A (4.6 mm and 5.8 mm) despite increased serum levels of oestradiol. At days +2 to +4, the endometrium was thicker in groups B and C together (7.2 mm) compared with group A (5.3 mm).     

Lymphocyte subset distribution and natural killer activity in growth hormone deficiency before and during short-term treatment with growth hormone releasing hormone

Natural killer (NK) cell activity was assessed in the peripheral blood of 20 patients with growth hormone (GH) deficiency due to a hypothalamic deficit of GH-releasing hormone (GHRH). All patients failed to respond to at least two provocative tests of GH secretion (GH below 7 ng/ml) but responded to a single GHRH iv bolus injection (1 microgram/kg body wt). In 14 of the 20 patients (20 determinations), lymphocyte subsets were also measured; in all patients the distribution of lymphocyte subsets was within the normal range. More importantly, NK cell activity in the 20 patients was significantly lower than in controls (P less than 0.01). To assess the in vivo effect of GH and GHRH on NK activity and lymphocyte subset distribution, immunologic tests were performed (i) before and after a single iv bolus injection of GHRH (1 microgram/kg body wt) in six patients; (ii) before and after 3 weeks of GHRH treatment (3-9 micrograms/kg body wt, one to four times daily) in five patients; and (iii) after 6 weeks of GH treatment (5 IU sc every alternate day) in one patient. Neither NK activity nor the distribution of lymphocyte subsets was altered during short-term GHRH administration. In conclusion, low NK activity is found in GH-deficient patients, and short-term administration of GH or GHRH fails to restore this immunological abnormality. This result suggests that the hypothalamus may be a regulator of NK activity in the human and that patients with hypothalamic deficiencies should be monitored for the development of discrete immunodeficiencies.     

The 3C syndrome: Evolution of the phenotype and growth hormone deficiency

The 3C syndrome (cranio-cerebello-cardiac dysplasia or the Ritscher-Schinzel syndrome) is a recently delineated condition involving abnormalities of the cranium (large head with prominent forehead), cerebellum (Dandy-Walker cyst and vermis hypoplasia), and cardiac (primarily septal) defects. At least 20 individuals with this condition have been reported in the past 11 years. We report on a girl with the 3C syndrome who at 13 years of age is the oldest patient reported to date. She has been followed since birth, allowing us to show the evolution of her phenotype over time. In addition, she has documented growth hormone deficiency. We suggest that growth hormone deficiency should be considered as a possible cause of the short stature often seen in this condition. Am. J. Med. Genet. 87:61–64, 1999. © 1999 Wiley-Liss, Inc.     

Expanding the phenotype of biallelic RNPC3 variants associated with growth hormone deficiency

Pathogenic variants in components of the minor spliceosome have been associated with several human diseases. Recently, it was reported that biallelic RNPC3 variants lead to severe isolated growth hormone deficiency and pituitary hypoplasia. The RNPC3 gene codes for the U11/U12‐65K protein, a component of the minor spliceosome. The minor spliceosome plays a role in the splicing of minor (U12‐type) introns, which are present in ~700–800 genes in humans and represent about 0.35% of all introns. Here, we report a second family with biallelic RNPC3 variants in three siblings with a growth hormone deficiency, central congenital hypothyroidism, congenital cataract, developmental delay/intellectual deficiency and delayed puberty. These cases further confirm the association between biallelic RNPC3 variants and severe postnatal growth retardation due to growth hormone deficiency. Furthermore, these cases show that the phenotype of this minor spliceosome‐related disease might be broader than previously described.