Presurgical octreotide treatment in acromegaly: no improvement of final growth hormone (GH) concentration and pituitary function. A long-term case-control study

Summary Background. The effect of presurgical long-acting somatostatin analogue (SSA) treatment on operative outcome in acromegaly is as yet uncertain and long-term observations are lacking. We evaluated in an acromegaly case-control study the effect of octreotide pre-treatment on short- and long-term postoperative GH concentrations, pituitary function and glucose tolerance.Methods. 48 patients with a pituitary macro-adenoma – micro- and giant adenomas excluded – were evaluated. 24 patients received presurgical octreotide treatment (secondary surgery, prospectively studied). Another 24 thoroughly matched patients had been operated on without prior octreotide therapy (primary surgery, retrospective evaluation). No patient had received any other treatment prior to operation/octreotide. Standardized testing was performed at diagnosis, following octreotide treatment, after surgery and then yearly for 10.3±0.9yrs (mean±SE, primary surgery) and 4.1±0.6yrs (secondary surgery). Immediate and 4-year postoperative results were compared. All work-up was strictly identical in both groups, except for imaging techniques. Partial remission was defined as mean GH profile (6-h/7-point) concentration <2.5µg/L, and complete remission as GH nadir <1µg/L during OGTT plus normal IGF-I concentration (when available).Findings. The median profile GH (µg/L) values and the OGTT GH nadir values post-surgery (2.4/1.0 vs 1.8/0.7, primary and secondary surgery, resp.) as well as 4yrs later (2.1/1.15 vs 2.3/0.8) were not significantly different between the groups. The 10-year results of the primary surgery group were not significantly different from its 4-year results. Subgroup analysis of pre-treated patients revealed no significant difference between those with and without tumour shrinkage, or between those with and without parasellar tumour extension. Postoperatively pituitary function was not significantly different between the groups. After 4-years the pituitary-adrenal axis was slightly more impaired in the secondary surgery group rather than following primary surgery, while the pituitary-gonadal axis was not different.Conclusion. Presurgical octreotide treatment has no significant short- or long-term beneficial effect on GH concentration or pituitary function.     

Use of chlorpromazine in the treatment of adynamic ileus

Ten patients suffering from severe adynamic ileus which did not respond to standard treatment, consisting of nasogastric suction and neostigmine, received chlorpromazine either intravenously or intramuscularly in association with neostigmine. This therapy was successful in 8 patients and failed in 2. One 89-year-old woman developed a cecal perforation. This complication could presumably have been avoided with a blow hole cecostomy.Résumé Dix malades atteints d'un iléus paralytique grave ne répondant pas au traitement classique-aspiration gastrique et néostigmine-ont été traités à la chlorpromazine intraveineuse ou intramusculaire associée à la néostigmine. Le traitement a été efficace dans 8 cas; il a échoué dans 2 cas. Une malade de 89 ans a présenté une perforation caecale qui aurait vraisemblablement pu Être évitée par une caecostomie de décharge.Supported by the Fonds de la Recherche Scientifique et Médicale.     

Correlation among plasma osteocalcin,growth hormone,and somatomedin C in acromegaly

Summary Plasma osteocalcin (BGP), growth hormone (GH), and somatomedin C(SmC) were measured in 12 patients with acromegaly [7 clinically active (aA), 5 cured (cA)] and 9 control subjects (C). Basal plasma values for the three parameters were higher in aA than in C and in cA. No significant difference was found between cA and C. A significant linear correlation between BGP and GH and between BGP and SmC was obtained. These results suggest an effect of GH on BGP synthesis, possibly mediated by SmC, although a direct effect of GH on bone cannot be exclulded.     

Plurihormonal pituitary adenoma with concomitant adrenocorticotropic hormone (ACTH) and growth hormone (GH) secretion: a report of two cases and review of the literature

Plurihormonal pituitary adenomas are tumours that show immunoreactivity for more than one hormone that cannot be explained by normal adenohypophysial cytodifferentiation. The most common combinations in these adenomas include growth hormone (GH), prolactin (PRL) and one or more glycoprotein hormone sub-units (β-TSH, β-FSH, β-LH and αSU). The authors report two cases of a plurihormonal pituitary adenoma expressing the rare combination of ACTH and GH. They both underwent successful transphenoidal hypophysectomy (TSH). Long-term post-operative follow-up revealed no evidence of tumour recurrence. Due to the multiple secretions and plurihormonal characteristics clinical diagnosis of composite pituitary adenomas can be difficult. The authors discuss the diagnosis and management of composite pituitary adenomas and review the literature regarding this rare phenomenon.     

Contribution of growth hormone-releasing hormone and somatostatin to decreased growth hormone secretion in elderly men.

OBJECTIVE: The pathophysiology of the decline in circulating growth hormone (GH) concentrations that may occur with ageing remains elusive. We have investigated the potential contributions of decreased endogenous GH-releasing hormone (GHRH) and increased somatostatin secretion to this phenomenon. DESIGN AND METHODS: The strategy used was to stimulate GH secretion in 8 young (20-24 years old, body mass index (BMI) 22.8 +/- 2.8 kg/m2) and 8 elderly (68-82 years old, BMI 23.4 +/- 1.6 kg/m2) male subjects on separate occasions by means of: (i) intravenous bolus 0.5 microgram/kg D-Ala2 GHRH(1-29)-NH2 alone; (ii) 0.5 microgram/kg GHRH after pre-treatment with two oral doses of 50 mg atenolol (to inhibit somatostatin secretion); (iii) 1.25 mg oral bromocriptine alone (to increase endogenous GHRH and/or inhibit somatostatin); (iv) 50 mg oral atenolol plus 1.25 mg oral bromocriptine; and (v) 0.5 microgram/kg GHRH after pre-treatment with 1.25 mg oral bromocriptine. RESULTS: The elderly men had a significantly lower peak and area under curve (AUC) GH response to intravenous GHRH when compared with 8 young men (peak 3.1 +/- 1.0 ng/ml v. 21.6 +/- 5.0 ng/ml, AUC 205 +/- 56 ng/ml/min v. 1,315 +/- 295 ng/ml/min, P < 0.05). Pre-treatment with atenolol before GHRH administration produced no significant increase in peak and AUC GH response in both groups, which remained lower in the elderly men than in their young counterparts (peak 5.5 +/- 1.8 ng/ml v. 29.3 +/- 7.0 ng/ml, AUC 327 +/- 90 ng/ml/min v. 2,017 +/- 590 ng/ml/min, P < 0.05). Bromocriptine alone did not cause a significant rise in GH concentration in either elderly or young subjects (peak 3.1 +/- 1.1 v. 8.8 +/- 3.2 ng/ml, P > 0.05). When atenolol was administered before bromocriptine, both groups responded but the elderly subjects had a significantly greater peak and AUC response (peak 3.6 +/- 0.7 v. 10.7 +/- 2.1 ng/ml; AUC 191 +/- 39 v. 533 +/- 125 ng/ml/min, P < 0.05). Bromocriptine given before GHRH failed to potentiate GHRH action on GH release in either group. Of 5 elderly men who underwent further evaluation of GH secretory ability, 2 subjects had GH levels > 10 ng/ml, either basally or after intravenous GHRH. The remaining 3 had an initially impaired GH response to bolus intravenous GHRH. After 100 micrograms GHRH subcutaneously twice daily for up to 2 weeks the GH responses to intravenous bolus GHRH (0.5 microgram/kg) were reassessed. One exhibited a normal response (> 10 ng/ml) after 1 week of daily GHRH treatment, another had a near-normal response after 2 weeks (9.7 ng/ml), while the third still had an impaired response by the end of the 2-week treatment period (3.2 ng/ml). CONCLUSIONS: The restoration of endogenous GH secretion in these elderly subjects by means of GHRH priming, and the failure of manipulation of somatostatinergic tone to restore a normal GH response to GHRH suggests that somatotroph atrophy due to a reduction in endogenous GHRH secretion is the principal cause of the diminished GH secretion with ageing.     

Detailed studies of growth hormone secretion in cystinosis patients

Background

Cystinosis is an autosomal recessive disorder characterized by intralysosomal cystine accumulation. Growth retardation is more pronounced in cystinosis than in other chronic kidney diseases and is mostly not corrected by cysteamine.

Methods

Growth was evaluated in nine cystinosis patients, all treated with cysteamine, both after cysteamine and recombinant human growth hormone (rhGH) therapy initiation. Growth hormone (GH) secretion was studied by nocturnal GH measurements in four of nine patients and by glucagon test in four of nine patients.

Results

RhGH was administered to seven of nine patients. At rhGH initiation, height was below ?2 SDS in five of seven patients, final height was above ?2 SDS in six of seven. In two patients not treated with rhGH, final height remained below ?4 SDS despite cysteamine treatment being started at the age of 6.1 and 8.1?years, respectively. Nocturnal GH secretion was normal in all patients. Glucagon tests revealed GH deficiency in one patient; two of four patients had abnormal GH peak timing.

Conclusions

We present the first reported case of GH deficiency in cystinosis. Although no overt GH deficiency was detected in other patients, abnormal GH peak timing can indicate a subclinical GH secretion problem. RhGH significantly improved growth in cystinosis patients and should be initiated early in life.     

Changing patterns of insulin-like growth factor-I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly

OBJECT: According to a recent consensus statement on the treatment of acromegaly, its biochemical cure is defined as the normalization of age- and sex-adjusted insulin-like growth factor (IGF)-I levels and the suppression of growth hormone (GH) by glucose to lower than 1 ng/ml. The present study was prompted by the clinical observation that many cases of acromegaly can be considered cured according to one criterion but not others at different moments in a patient's postoperative course. METHODS: Fifty-three patients with acromegaly (30 women and 23 men) harboring nine microadenomas and 44 macroadenomas were evaluated after surgery by assessing age- and sex-adjusted IGF-I levels as well as glucose-suppressed GH levels. Fifty of these patients were studied more than once during follow up. Acromegaly was categorized as cured if the patient's IGF-I level was normal and their glucose-suppressed GH level was lower than 1 ng/ml; the disease was considered to be active if the patient's IGF-I level was high and the GH nadir was higher than 1 ng/ml following administration of glucose. Discordant categories of the disease were found in patients with high IGF-I levels and a GH nadir lower than 1 ng/ml after glucose administration and in those with normal IGF-I levels and a GH nadir higher than 1 ng/ml after glucose intake. At the first postoperative biochemical evaluation (1-3 months), 34% of patients harboring macroadenomas were classified as having been cured of acromegaly, 39% as having the active disease, and 27% as having the discordant form of the disease. When last evaluated (> or = 12 months postoperatively), the percentage of patients with the discordant form dropped to 14% and the proportion of cases cured and active was 44% and 41%, respectively. Of the nine patients with microadenomas, 44.4% were cured of acromegaly, 33.2% had the active disease, and 22% had the discordant variety on first evaluation. Twelve months or longer after transsphenoidal surgery, 55.5% of cases were cured, 11.1% were active, and 33% were discordant. In most cases, the discordant variety developed because of a persistently elevated level of IGF-I, followed by an incompletely suppressed GH level. Nineteen patients (38%) modified their biochemical category. In 15 of these patients this change in category was due to a change in IGF-I levels, becoming normal in 12 patients and rising to above normal range in three. A tumor remnant was demonstrated on magnetic resonance images in only four of these 19 patients. CONCLUSIONS: The authors conclude that the discordance rate between the biochemical markers that define cure in acromegaly is higher than previously reported, and the biochemical status assigned to a patient early in the postoperative course is very likely to change later, particularly when initially discordant.     

Stimulation of growth hormone secretion in children with X-linked hypophosphatemia

X-linked hypophosphatemia is characterized by low serum phosphorus, relative vitamin D deficiency and rickets. Despite adequate metabolic control with oral phosphate and vitamin D therapy, patients with X-linked hypophosphatemia have short stature. Whether growth hormone (GH) deficiency plays a role in short stature in patients with X-linked hypophosphatemia is not known. The purpose of this report was to investigate the response of GH to sequential paired pharmacological stimulation in patients with X-linked hypophosphatemia. Basal GH was 3.8±0.7 ng/ml, insulin-like growth factor-I (IGF-I) was 225±38 ng/ml and IGF binding protein-3 was 3.0±0.2 mg/l in 16 children studied with X-linked hypophosphatemia. In response tol-dopa and arginine hydrochloride stimulation, serum GH rose to above 7 mg/ml in all patients. Thus, the short stature in patients with X-linked hypophosphatemia is not due to a GH/IGF-I secretory defect.     

重组生长激素在外科手术后呼吸衰竭治疗中的应用

目的探讨外科手术后呼吸衰竭的患者应用重组生长激素 (rhGH)的效果。方法 80例外科手术后常规停用呼吸机失败的患者 ,按疾病种类分为rhGH组和对照组各 40例 ,rhGH组肌注rhGH 8IU/d。结果机械通气时间在rhGH组平均为 (30± 12 )d ,对照组平均为 (39± 13)d ,t=2 5 38,P <0 0 1。rhGH组血清白蛋白浓度治疗前为 (30± 5 )g/L低于治疗第 8天 (39± 7)g/L ,t=2 6 19,P <0 0 1。rhGH组预测死亡率为 45 % ,实际死亡率为 15 % ,t=1 884,P <0 0 5。结论应用rhGH可缩短外科手术后危重患者机械通气时间 ,使患者成功脱离机械通气 ,降低死亡率     

神经外科抗利尿激素异常分泌综合征的诊治

目的探讨神经外科中抗利尿激素异常分泌综合征(SIADH)诊断、鉴别诊断及其治疗.方法对6例SIADH患者的临床表现、治疗经过、确诊过程进行回顾性分析总结.结果 SIADH病人特点(1)低血钠(血钠≤128 mmol/L),补钠越多,尿排钠越多,24 h尿钠与每日补充的钠总量持平;(2)ADH测定对SIADH与CSWS无鉴别意义;(3)无血容量增多或水肿表现;(4)限水治疗有效.结论 SIADH诊断及与CSWS的鉴别诊断十分困难,临床采用试验性限水限钠疗法,即是鉴别诊断的重要手段,又是SIADH治疗的有效方法.     

Insulin-like growth factor 1 (IGF-1) and growth hormone (hGH) as the markers of osteoarthritis

AIM OF STUDY: The aim of study was evaluation of diagnostic usefulness of IGF-1 and hGH serum level in osteoarthritis. MATERIAL AND METHODS: IGF-1 and hGH concentration were measured in serum collected from 25 patients with coxarthrosis and 16 healthy persons. IGF-1 and hGH serum level were assayed by ELISA. RESULTS: There was no statistics difference in growth hormone serum level between osteoarthritis patients and healthy persons. The ROC curve for hGH concentration confirmed low discriminatory value of this test. There was no significant correlation between hGH and IGF-1 in serum. IGF-1 concentration in patients serum was significant lower then in control grupe. The ROC curve for serum level of IGF-1 confirmed significant usefulness this test in laboratory diagnostic of osteoarthritis. CONCLUSIONS: Serum concentration of IGF-1 seems to be usefull laboratory marker of osteoarthritis.