Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten acromegalic patients were treated with the somatostatin analogue SMS 201-995 (SMS) for 3-38 weeks in various doses and by different administration routines (thrice daily or multiple sc injection). Plasma GH daily profiles, plasma IGF-I, urinary GH, serum TSH, IRI and fasting blood glucose (FBG) concentrations were measured before and during SMS treatment. Plasma GH rapidly decreased within one hour in all patients and was suppressed for at least 4 h after a 50 micrograms sc injection of SMS in 8 patients. Multiple injections of 300-600 micrograms/day SMS (25-50 micrograms X 12) suppressed GH throughout the day. Plasma IGF-I was completely normalized in 4 patients, and, in all but one of the others, decreased markedly. Urinary GH decreased within the first week of treatment in all patients and normalization was obtained in 3 patients. Shrinkage of the pituitary tumor, as determined by CT or MRI, was observed in 7 of 9 patients. Other clinical improvements, such as diminution or complete disappearance of swelling of soft tissues, excessive perspiration, and headache, were observed in 7 of 8 patients. Changes in serum TSH, IRI and FBG were seen in 3-4 patients, but without any apparent clinical problems. In conclusion, SMS is a useful clinical tool for treatment of acromegaly, and a multiple sc injection method seems to be preferable.
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PMID:Treatment of acromegaly with long acting somatostatin analogue SMS 201-995. 322 51

The purpose of this study was to determine the effects of recombinant human GH (rhGH; 0.025 mg/kg.day) and one of two doses of recombinant human insulin-like growth factor-I (rhIGF-I; 0.015 and 0.060 mg/kg, twice daily) on body composition in elderly women. Sixteen healthy elderly women (mean age +/- SEM, 71.9 +/- 1.3 yr) were randomly assigned to receive either rhGH (GH; n = 5), low dose rhIGF-I (n = 6), or high dose rhIGF-I (n = 5). A 2-week predrug baseline period was followed by 4 weeks of hormone treatment, with a standardized diet fed throughout. All groups experienced a significant increase in serum IGF-I and IGFBP-3 levels over the treatment period, accompanied by significant decreases in IGF-II (P < 0.05). Fat mass decreased in all groups, with significant increases in lean body mass and nitrogen retention occurring in the high dose IGF and GH groups. Total body water did not change, whereas increases observed in intracellular fluid approached significance (P = 0.06). These anabolic changes were accompanied by numerous negative side-effects in the GH and high dose IGF groups, including headaches, lethargy, joint swelling/pain, and bloatedness. The low IGF dose was well tolerated. These results demonstrate that the administration of rhGH and rhIGF-I for 4 weeks results in anabolic changes in body composition in elderly women.
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PMID:The effects of recombinant human insulin-like growth factor-I and growth hormone on body composition in elderly women. 753 17

Active acromegaly displays high morbidity and mortality. It should be treated aggressively with surgery, radiotherapy and medical therapy. In order to confirm the effectiveness and tolerability of octreotide in refractory acromegaly, we studied six patients after unsuccessful transsphenoidal surgery, or surgery and conventional radiotherapy performed for pituitary macroadenomas. After nuclear magnetic resonance imaging and hormonal studies, they were submitted to octreotide therapy (100 micrograms subcutaneously every eight hours), reevaluated every six weeks for six months, and followed-up for further six months. A clear reduction of subjective symptoms including headache was noticed. Two patients, however, suffered from recurrent malaise and reduced octreotide doses (one case, who also developed cholelithiasis), or refused to continue the treatment. GH and IGF-I levels were normalized (1 patient), improved (3 patients) or unmodified (2 patients). Not every acromegalic patient responds to low-dose octreotide therapy with normalization of GH levels. In selected cases, however, octreotide may be usefully employed for active acromegaly in support of surgery and radiotherapy.
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PMID:Octreotide in the management of active acromegaly due to inoperable growth hormone-secreting adenoma. 818 74

Thirty-one patients with growth hormone insensitivity syndrome (GHIS) and 2 with GH gene deletion (age 11.2 (3.7-22.9) years; BA (GP) 8.2 years; height -6.5 +/- 1.6 SDS) were recruited for the multicenter study. At birth, length was more retarded (-1.38 SDS) than weight (-0.56 SDS). The rhIGF-I dose was 40-120 micrograms/kg BW twice daily s.c. In 26 patients, first year HV increased from 3.9 +/- 1.8 to 8.5 +/- 2.1 cm/year (delta (d) HT SDS 0.8 +/- 0.5). In 18 patients, second year HV was 6.4 +/- 2.2 cm/year (dHT SDS 0.4 +/- 0.5). There was normal progression of puberty. Mean progression of BA was 1.2 and 1.5 years/year during the first and second year. There was no dose effect of IGF-I on growth. Weight-for-height index (WHI) and skinfold thickness were significantly correlated at start, 12 and 24 months (r = 0.83, 0.87 and 0.79). Changes in WHI were positively correlated with dHT SDS during the first and second year (r = 0.54, 0.56). Serum IGF-I rose, IGF-II decreased, and IGFBP-3 remained constant. Adverse events were (number of occasions): headache (21) (early); hypoglycemia (13); papilloedema (1) (reversible); Bell's palsy (1) (reversible); lipohypertrophy (7) (late); tonsillectomy/adenoidectomy (3) (late). The results show that there is effective long-term treatment of GHIS with systemically administered IGF-I and support the view that IGFBPs play an important role in the action of IGF-I.
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PMID:Insulin-like growth factor I improves height in growth hormone insensitivity: two years' results. 880 10

Medical therapy is frequently needed to normalize growth hormone/insulin-like growth factor I secretion in acromegaly. The aim of this study was to determine the long-term effects of the slow-release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who completed the 12-month period. A drug-related decrease in GH/IGF-I levels was observed. Basal GH/IGF-I levels were significantly (P < 0.001) reduced at 12 months, IGF-I was normalized in 35% of patients and GH levels were < 5 micrograms L-1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft-tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.
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PMID:Clinical results of long-term slow-release lanreotide treatment of acromegaly. 913 75

This single-center open sequential study aimed at comparing the efficacy of a 6-month treatment with lanreotide (LAN) (60-90 mg/month i.m.), to that of octreotide (OCT) (0.3-0.6 mg/day s.c.) in 45 patients with active acromegaly (GH, 63.2+/-12.1 ng/ml, IGF-I, 757+/-67.1 ng/ml). After 6 months of OCT treatment, safe GH (fasting <2.5, glucose suppressed <1 ng/ml) and IGF-I (normalized for age) levels were achieved in 23 patients. After treatment withdrawal, GH levels significantly increased in all patients, though remaining slightly lower than pre-OCT therapy (39.2+/-5.8 ng/ml) while plasma IGF-I levels were unchanged (654+/-59.4 ng/ml). After 6 months of LAN treatment, safe GH and IGF-I levels were achieved in 26 patients (57.7%). After OCT or LAN treatments, no significant difference was found between nadir GH (6+/-1 vs 5.9+/-1.1 ng/ml) and IGF-I levels (281+/-23.3 vs 262+/-20.6 ng/ml). Four out of the 20 patients poorly responsive to OCT achieved safe GH and IGF-I levels after LAN treatment. Among the 20 non-operated patients, a significant tumor shrinkage was documented by CT and/or MRI in 5 patients after OCT and in 1 patient after LAN treatment. All patients referred a notable improvement of soft tissue swelling, arthralgia, headache and weakness, both after OCT and LAN treatments. During the first days of OCT treatment, abdominal discomfort was referred by 12 patients and steatorrhea by 5 patients: side effects disappeared spontaneously in 6 cases while during treatment with pancreatic enzymes in the remaining ones. After the first injections of LAN, abdominal discomfort was referred by 10 patients and steatorrhea by 2 of them. No difference in the prevalence of both early and late side effects was noted after treatment with OCT and LAN (chi2, 0.49). The majority of these poorly tolerant patients had side effects with both compounds. During LAN treatment, side effects were mild and spontaneously disappeared but recurred after the injection of the drug in six patients. Gallstones were detected in one patient during OCT and in another during LAN, sludge was noted in 6 patients after OCT and in 2 after LAN treatment. In conclusion, the treatment with LAN allowed to achieve safe GH and IGF-I levels in 57.7% of acromegalics with an excellent patients' compliance. LAN treatment possessed similar efficacy and caused side effects with a similar incidence of OCT treatment. The recurrence of side effects after LAN injection suggests the necessity of a careful monitoring of adverse reactions.
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PMID:Effectiveness and tolerability of slow release lanreotide treatment in active acromegaly. 1009 Jan 36

A European multicentre, open-label 12-month study with Sandostatin LAR administered intramuscularly at 4-week intervals was initiated in 151 acromegalics responsive to octreotide. All patients received 3 injections of the 20 mg dose, following which the dose was adjusted to 10 mg in patients with mean 4-hour GH serum concentrations below 1 microgram/L (N: 29) and to 30 mg in patients with concentrations above 5 micrograms/L (N: 22). The GH level suppression was significant in the 20 mg dose group (p < 0.01) and for all 151 patients (p < 0.004), and was consistently maintained in all patients for the duration of the study. The suppression of the mean serum GH concentration to below 2.5 micrograms/L was recorded in 69.8% of patients at the endpoint treatment with Sandostatin LAR and 65.8% during prior treatment with Sandostatin s.c. A consistent suppression of serum IGF-I levels was also achieved. The number of patients with headache, fatigue, perspiration, joint pains and paresthesias had decreased significantly (p < 0.05) after the 6t]h injection of Sandostatin LAR vs. previous s.c. treatment. No patient discontinued the study because of drug-related adverse events. The most frequently reported adverse events were mild diarrhea, abdominal pain and flatulence. The local tolerability was very good. No impairment of safety hematology, biochemistry and thyroid function tests and no increased incidence of gallstone formation was recorded. Well tolerated and at least as efficacious as the s.c. formulation, Sandostatin LAR might become an alternative primary treatment to pituitary surgery and radiotherapy.
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PMID:Results of a European multicentre study with Sandostatin LAR in acromegalic patients. Sandostatin LAR Group. 1108 Nov 88

New depot somatostatin analogs such as lanreotide-slow release (LAN) represent a significant improvement in the medical treatment of acromegaly. Seventy-three consecutive acromegalic patients, treated by LAN, were evaluated in a retrospective monocentric study. Sixteen were excluded from further evaluation due to combined treatment with dopamine agonist drugs, early LAN withdrawal for persistence of headache, or gastrointestinal side-effects. Fifty-seven patients (aged 20-82 years, 16 males) were thus evaluated. Thirty-two patients had been previously treated by neurosurgery (Tx) and/or radiotherapy (Rx). After washout, LAN (30 mg) was administered im at 10-14-day intervals. Time intervals between injections were then individually tailored to normalize IGF-I levels. LAN was administered for 12 (6-36) [median (range)] months. GH and IGF-I levels decreased from 13 (7-20) [median (interquartile)] microg/l to 3.2 (1.7-6.2) microg/l (p<0.0001) and from 780 (596-1000) microg/l to 264 (180-530) microg/l (p<0.000001), respectively. Seven patients were resistant to treatment. Among the 50 sensitive patients, GH levels fell below 2.5 microg/l in 52% (and below 1 microg/l in 18%), IGF-I levels normalized in 72% and both results were obtained in 46%. IGF-I values normalized in 87% of patients treated every 14 days, in 100% every 21-28 days, in 69% every 10 days and in 22% every 7 days. No different control of GH/IGF-I hypersecretion was evidenced between patients previously treated or not by Tx and/or Rx. Patients with the lowest basal hormonal levels and those over 55 years showed greater responsiveness (both p<0.05). The maintenance of LAN schedule up to 18 months determined a further suppression (p=0.04 for IGF-I). A reduction of tumor size was shown in 60% of evaluated patients (6/10). HbA1c slightly increased in 42% of patients and gallstones were observed in 16%. LAN is a very effective tool in the treatment of acromegaly: its chronic administration normalizes GH/IGF-I levels in most patients, shrinks the tumor in a high percentage of patients and seems to control hormonal hypersecretion as primary treatment as well as neurosurgery.
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PMID:GH/IGF-I normalization and tumor shrinkage during long-term treatment of acromegaly by lanreotide. 1138 6

The aim of this study was to verify whether treatment with slow-release lanreotide (SRL) before surgery is useful in the management of patients with GH-secreting pituitary macroadenoma. Twenty untreated acromegalics were enrolled randomly in two groups. Ten patients (group 1: 2 males and 8 females aged 44.5 +/- 4.3 years) underwent surgery via transsphenoidal access. Only one of them was cured by surgery, whereas the other nine were treated with SRL. In the other ten patients (group 2: 3 males and 7 females aged 43.2 +/- 12.3 years), transsphenoidal surgery followed SRL treatment. Surgery induced the normalization of GH and IGF-1 levels in four group 2 patients - three of them had shown an evident shrinkage of the tumor after SRL treatment. After surgery, group 1 showed a significant decrease of mean IGF-1 (580 +/- 63 vs. 789 +/- 64 ng/ml, p < 0.02), but not of GH values (26.1 +/- 9.8 vs. 44.8 +/- 19.3 ng/ml, NS); the cured patient was excluded from the following evaluations. Group 2 showed an evident, but not significant, decrease of both GH and IGF-1 values compared to values measured at the end of medical treatment (GH: 22.4 +/- 9.7 vs. 7.7 +/- 4.7 ng/ml, NS. IGF-1: 570 +/- 69 vs. 402 +/- 58 ng/ml, NS). Gonadal, thyroid and adrenal impairment was evident in six, four and no patients in group 1 and in three, two and one patients in group 2, respectively. SRL 30 mg was administered every 14 days for three months and then every 10 days until the 6th month. Before SRL treatment, mean GH and IGF-1 levels did not differ significantly in group 1 vs. group 2 (GH: 29.3 +/- 10.5 vs. 43.4 +/- 22.0 ng/ml; IGF-1: 633 +/- 38 vs. 778 +/- 83 ng/ml). In group 1, a significant decrease of serum GH, but not of IGF-1 levels, was achieved at the end of 1st trimester of SRL (GH: 17.6 +/- 5.4 ng/ml, p < 0.05. IGF-1: 540 +/- 48 ng/ml, NS), whereas a significant decrease in both GH and IGF-1 values was evident during the 2nd trimester (GH: 6.1 +/- 3.0 ng/ml, p < 0.05. IGF-1: 433 +/- 74 ng/ml, p < 0.02). Serum GH levels, measured during the 2nd trimester of SRL therapy, were also significantly lower than levels measured at the end of the 1st trimester (p < 0.05). Group 2 serum GH and IGF-1 levels were not significantly decreased at the end of the 1st trimester (GH: 27.2 +/- 12.1 ng/ml, NS. IGF-1: 698 +/- 74 ng/ml, NS), whereas only serum IGF-1 (570 +/- 69 ng/ml, p < 0.05) was significantly reduced during the 2nd trimester of SRL (GH: 22.4 +/- 9.7 ng/ml, NS). Serum GH and IGF-I fell in the normal range in 4 patients in group 1 and one in group 2 at the end of the second trimester of SRL therapy. Independently of the trial applied, the mean clinical score level ameliorated significantly in both groups (group 1: p < 0.0005; group 2: p < 0.0001). In both groups, the proportion of patients complaining of headache and tissue swelling and the score level of headache, tissue swelling and excessive sweating decreased significantly. In group 1 the score level of fatigue and arthralgia also decreased significantly. In conclusion, this study proves that in patients with GH-secreting pituitary macroadenoma: (i) surgery followed by SRL induces a better clinical and biochemical status than SRL alone; (ii) SRL treatment before surgery ameliorates the clinical and biochemical outcome and reduces the prevalence of hypopituitarism due to surgery.
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PMID:Effectiveness of slow-release lanreotide in previously operated and untreated patients with GH-secreting pituitary macroadenoma. 1160 83

Stereotactic radiosurgery by gamma-knife (GK) is an attractive therapeutic option after failure of microsurgical removal in patients with pituitary adenoma. In these tumors or remnants of them, it aims to obtain the arrest of cell proliferation and hormone hypersecretion using a single precise high dose of ionizing radiation, sparing surrounding structures. The long-term efficacy and toxicity of GK in acromegaly are only partially known. Thirty acromegalic patients (14 women and 16 men) entered a prospective study of GK treatment. Most were surgical failures, whereas in 3 GK was the primary treatment. Imaging of the adenoma and target coordinates identification were obtained by high resolution magnetic resonance imaging. All patients were treated with multiple isocenters (mean, 8; range, 3-11). The 50% isodose was used in 27 patients (90%). The mean margin dose was 20 Gy (range, 15-35), and the dose to the visual pathways was always less than 8 Gy. After a median follow-up of 46 months (range, 9-96), IGF-I fell from 805 micro g/liter (median; interquartile range, 640-994) to 460 micro g/liter (interquartile range, 217-654; P = 0.0002), and normal age-matched IGF-I levels were reached in 7 patients (23%). Mean GH levels decreased from 10 micro g/liter (interquartile range, 6.4-15) to 2.9 micro g/liter (interquartile range, 2-5.3; P < 0.0001), reaching levels below 2.5 micro g/liter in 11 (37%). The rate of persistently pathological hormonal levels was still 70% at 5 yr by Kaplan-Meier analysis. The median volume was 1.43 ml (range, 0.20-3.7). Tumor shrinkage (at least 25% of basal volume) occurred after 24 months (range, 12-36) in 11 of 19 patients (58% of assessable patients). The rate of shrinkage was 79% at 4 yr. In no case was further growth observed. Only 1 patient complained of side-effects (severe headache and nausea immediately after the procedure, with full recovery in a few days with steroid therapy). Anterior pituitary failures were observed in 2 patients, who already had partial hypopituitarism, after 2 and 6 yr, respectively. No patient developed visual deficits. GK is a valid adjunctive tool in the management of acromegaly that controls GH/IGF-I hypersecretion and tumor growth, with shrinkage of adenoma and no recurrence of the disease in the considered observation period and with low acute and chronic toxicity.
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PMID:Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. 1284 50


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