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PubMed2002

Growth hormone receptor antagonist improves insulin resistance in acromegaly.

Growth hormone hypersecretion is a known cause of insulin resistance. This change in insulin sensitivity is believed to be mediated directly by growth hormone binding to its receptor. Five subjects ages 28-55 years who were participating in a clinical study that had been designed to assess the effects of a growth hormone receptor antagonist (Pegvisomant) on disease activity in acromegaly were evaluated to determine the role of growth hormone hypersecretion in inducing changes in insulin sensitivity. These subjects were treated with the 15-30 mg/day of Pegvisomant for periods ranging from 14 to 23 months. These doses were adequate to normalize IGF-I in four of the five subjects. The subjects were monitored to ensure that there were no significant changes in diet, exercise, or weight. Mean pretreatment IGF-I was 1104+/-277 ng/ml and decreased to a nadir of 355+/-157 ng/ml on treatment. After a 6-week withdrawal period, mean IGF-I had increased to 549+/-142 ng/ml. Fasting insulin was 35.2+/-16 uU/ml prior to treatment then decreased to a nadir of 19.9+/-14.6 uU/ml on treatment and then increased to 24.5+/-11.3 uU/ml. Fasting glucose decreased from 187+/-68 to 122+/-38 mg/dl and then increased to 159+/-41 mg/dl. Hemoglobin A(1)C decreased from 8.1+/-1.7 to 6.3+/-1.5%. Two subjects with overt type II diabetes had decreases in hemoglobin A(1)C from 8.3 to 5.9% and from 11.4 to 8.6%. These changes were associated with decreases in the amount of medication needed to control blood glucose. Weight remained stable throughout the study. The results show that the Pegvisomant is an effective agent for improving insulin resistance in subjects who have acromegaly and that this effect is independent of weight loss. The results suggest a potential role for Pevisomant in the treatment of insulin resistant states other than acromegaly.

Acromegaly↗
PubMedDate not supplied

Biochemical definitions of disease activity in acromegaly.

UNLABELLED: In acromegaly the therapeutic outcome is difficult to assess and depends on the biochemical method. We have ascertained disease activity in 70 acromegalic patients by means of a GH profile (8 hourly samples) and a single IGF-I measurement as compared to a healthy control group. As an estimate of the "stiffness" of the GH profile we calculated the SD/nadir(GH) from the GH profile. In the control group the following upper normal limits were obtained: IGF-I (microg/l) 217; mean GH (microg/l) 2.16; nadir GH (g/l) 0.3. Based on ROC plot analysis a value of 2.0 for the SD/nadir ratio was used as cut-off. This translated into the following surgical cure rates (%): IGF-I 47; mean GH 77; nadir GH 65; SD/nadir 30. Some of the patients post-surgery had elevated IGF-I levels despite "normal" GH levels. Abnormal SD/nadir versus normal IGF-I and vice versa were recorded in many patients post-surgery. IN CONCLUSION: (1) cure rates of acromegaly depend strongly on the criteria being used and (2) estimates of GH secretion pattern may yield important information about GH status in acromegaly.

Acromegaly↗
PubMed1988

Acromegaly--the mucosal changes within the nose and paranasal sinuses.

The presence of upper respiratory tract obstruction in patients with acromegaly has been described. The main sites for obstruction were previously thought to be laryngeal and oropharyngeal. This study reviews 65 patients with acromegaly and 27 patients with a prolactinoma treated by trans-ethmoidal hypophysectomy. The results confirmed a very high incidence of polyp formation and mucosal hypertrophy within both the sphenoid (88 per cent) and ethmoidal (62 per cent) sinuses of the acromegalic patients. The histological appearances of the mucosal hypertrophy and polyposis confirmed no specific features attributable to acromegaly. Patient age and serum H.G.H. level do not appear to be significant factors. These findings within the para-nasal sinuses have never previously been reported.

Acromegaly↗
PubMed1997

Acromegaly with normal basal growth hormone levels.

BACKGROUND: The most common cause of acromegaly is excess of growth hormone (GH) secretion. METHODS: We report a 42-year-old male patient, who had become acromegalic over the past 5 years. There were no visual changes or change in sexual function, no gynaecomastia or galactorrhoea. Both CT and MRI scans showed a large mass measuring 2.5 x 2.5 x 3.5 cm, originating from the sella turcica and extending into and totally filling up the sphenoid sinus with diffusely invasive features. RESULTS: Basal serum GH level was within normal range, but insulin-like growth factor 1 (IGF-1) was elevated with slightly increased prolactin (PRL) and impaired GH secretory regulation as well. A pituitary adenoma was partially removed through transsphenoidal microsurgery. Pathology confirmed a mammo-somatotrophic adenoma but immunocytochemistry study of the tumour showed only positivity for PRL but not GH. CONCLUSIONS: When acromegaly occurs without GH level elevation, one should pay attention that: 1) IGF-1 might be the cause of the clinical feature of acromegaly; 2) The tumour might undergo morphological transformation; and 3) Hyperinsulinemia or GH receptor antibody formation could also be the cause of the acromegalic appearance.

Acromegaly↗
PubMed2000

Lanreotide 60 mg, a longer-acting somatostatin analog: tumor shrinkage and hormonal normalization in acromegaly.

BACKGROUND: Somatostatin analogues are nowadays the milestone in the medical treatment of acromegaly. We evaluated the effects of a new 60 mg longer-acting formulation of lanreotide (LAN60) on GH/IGF-I levels and tumor size. PATIENTS: Twenty-one acromegalics entered a prospective monocentric open study. Eight were consecutive "de novo" patients (group I). Thirteen patients sensitive to SA (GH levels < 2.5 [mgr]g/l and/or IGF-I normalization on chronic LAN 30 mg (LAN30) treatment) were switched to LAN60 (group II). PROTOCOL: LAN60 was administered IM for 6 cycles at 28 day intervals. In group I when GH/IGF-I remained pathological, the intervals were shortened to 21 days for the last three cycles. CONTROLS: GH/IGF-I at the end of the 1st, 3rd and 6th cycle; MRI at the end of the study in all patients in group I bearing an adenoma. RESULTS: Group I. GH (p = 0.00638, below 2.5 [mgr]g/l in two patients) and IGF-I (p = 0.0289, normalized in 5) significantly decreased. In one of two patients shortening the LAN60 schedule was more effective in suppressing GH/IGF-I. Group II. No change in GH and IGF-I levels was observed with the administration of LAN60, instead of LAN30. On LAN60 GH remained below 2.5 [mgr]g/l in 8/10 patients and IGF-I normal in 11/11 patients that had attained those values on LAN30. Tumor markedly shrank (23% to 64% vs basal), from 1400 (664-1680) mm3 to 520 (500-960) mm3 (median, interquartile, p = 0.0218) in all the 5 evaluable patients. CONCLUSION: LAN60 is a very effective and longer-lasting formulation for the treatment of acromegaly. A closer administration schedule might achieve greater efficacy. Its effectiveness in shrinking tumor opens new perspectives in the therapy of acromegaly.

Acromegaly↗
PubMed2001

Gamma knife radiosurgery in the management of patients with acromegaly: a review.

Although acromegaly is a rare disease, the need for an effective treatment that is able to induce biochemical cure is an extremely important issue. Unsuccessfully treated acromegaly is associated with increased morbidity and an age-corrected mortality so that early and aggressive therapy to normalize hormonal levels should be instituted at diagnosis. Ideally, the growth hormone-secreting adenoma should be completely resected, with preservation or subsequent restoration of pituitary function. Patients with recurrence or failure after surgery are treated with a second surgery, medical, radiation treatment, or combined modality treatment. Steotactic radiosurgery with gamma knife allows the delivery of focused radiation in a single session to the pituitary tumor that delivers a more biologically effective dose to the tumor than fractionated radiotherapy. Its use as a primary or adjuvant treatment for acromegalics may be more cost effective than medical treatment in these patients. Although it seems to be very effective in controlling growth and secretion of the growth hormone-secreting pituitary adenomas, there is a chance that some major risks from gamma knife radiosurgery might occur. This article will review the role that gamma knife radiosurgery might have in patients with acromegaly.

Acromegaly↗
PubMed2002

Roles of insulin-like growth factor-I and growth hormone in mediating insulin resistance in acromegaly.

Most patients with acromegaly have some degree of insulin resistance. The principal mediator of insulin resistance in acromegaly is hypersecretion of growth hormone. Growth hormone acts at several levels to block insulin actions including inhibiting phosphorylation of the insulin receptor and one of its principal signaling molecules IRS-1 in response to insulin administration. This leads to reduced sensitivity to insulin in the periphery in stimulating peripheral glucose uptake and to increased resistance to insulin's ability to suppress gluconeogenesis. Furthermore growth hormone excess leads to mobilization of free fatty acids which inhibit insulin stimulated glucose oxidation by acting as a competitive energy source thus leading to further worsening of insulin resistance. These abnormalities can be overcome by administering agents which either lower growth hormone secretion or block growth hormone action. The role of elevated IGF-I in acromegaly in mediating insulin resistance is more difficult to analyze. Indirect inferences from the data that are available suggest that IGF-I is acting to enhance insulin sensitivity and partially counteracting the insulin antagonistic effects of growth hormone. In a recent study administration of IGF-I to acromegalics was shown to improve insulin sensitivity over and above the level that could be achieved by simply blocking growth hormone action. Therefore it appears that the net effect of IGF-I is to counterbalance some of the effects of growth hormone hypersecretion on insulin resistance.

Acromegaly↗
PubMed1977

An investigation into the pathogenesis of hypertension in acromegaly.

1. In 29 patients with acromegaly, plasma renin activity and growth hormone were measured during fasting and recumbency on free diet. Exchangeable sodium was measured in all cases and expressed as a percentage of the expected value on the basis of lean body mass. 2. Twenty-two control subjects without evidence of cardiovascular, renal or endocrine disease were studied in the same way. 3. There was a significant increase in exchangeable sodium and suppression of plasma renin activity in the acromegalic patients in comparison with control subjects. 4. There was a significant positive correlation between exchangeable sodium and plasma growth hormone. 5. Hypertensive acromegalic patients (diastolic blood pressure larger than or equal to 100 mmHg) tend to have a lower (although not significantly so) exchangeable sodium than normotensive subjects. 6. We conclude that (a) suppression of plasma renin activity in acromegaly can be explained by sodium retention, (b) hypersecretion of growth hormone is probably responsible for the increased exchangeable sodium, and (c) sodium overload cannot be directly related to blood pressure but may contribute to the increased occurrence of hypertension in acromegaly.

Acromegaly↗
PubMed2002

Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly.

BACKGROUND AND OBJECTIVE: The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy. PATIENTS AND METHODS: Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant. RESULTS: Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively). CONCLUSIONS: This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.

Acromegaly↗
PubMed2000

Acute leukaemia in acromegaly patients.

Acromegaly patients are known to have an increased risk of malignancies, especially colonic adenocarcinoma. This may be as a result of the growth-stimulating effect of growth hormone (GH). The clustering of leukaemia in children treated with GH has also caused concern. There have been a few reports of leukaemia in acromegaly patients. We report two patients with acute lymphoblastic leukaemia and one patient with acute myeloid leukaemia among 106 acromegaly patients treated over a 15-year period. Two of the cases received radiotherapy as part of their treatment. Adjusted for age and follow-up years, the incidence of leukaemia in this cohort is significantly higher than the general population. The incidence is also higher than would be expected as a result of radiotherapy alone, suggesting that GH may play a synergistic role.

Acromegaly↗
PubMed1997

Acromegaly or chronic renal failure: a diagnostic dilemma.

Uraemic patients may have markedly elevated serum GH concentrations yet, for hitherto unknown reasons, they do not develop acromegaly. We discuss the diagnostic dilemma presented by a 33-year-old Caucasian male with chronic renal failure (creatinine clearance 10 ml/min) secondary to polycystic kidney disease, elevated GH concentrations (fasting concentration of 22.6 rising to 77.9 mU/l 30 minutes after a 75-g oral glucose load) as well as acromegalic features. Review of the patient's relatives and the findings of a normal serum IGF-I concentration and a normal pituitary fossa on magnetic resonance imaging, suggest that the patient's acromegalic appearance is a familial trait and his abnormal GH dynamics a result of his renal failure rather than acromegaly. The patient's normal GH bioactivity and reduced GH binding protein concentration supports the current belief that chronic renal failure leads to an increase in peripheral tissue resistance to GH due to decreased GH receptor numbers. These changes, together with reduced IGF-I bioactivity, may explain why patients with chronic renal failure do not develop acromegaly in the presence of abnormally elevated levels of GH.

Acromegaly↗
PubMed1999

A comparison of lanreotide and octreotide LAR for treatment of acromegaly.

BACKGROUND AND OBJECTIVE: Two long-acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugs METHODS: We prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l. RESULTS: Five (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF-1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02). CONCLUSIONS: At current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe' (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.

Acromegaly↗
PubMed2000

Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.

BACKGROUND AND OBJECTIVE: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients. PATIENTS AND METHODS: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3. RESULTS: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated. CONCLUSION: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.

Acromegaly↗
PubMed2000

Optimal dosage interval for depot somatostatin analogue therapy in acromegaly requires individual titration.

BACKGROUND: The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10-14 days, respectively, are applicable to all patients. AIMS: To determine the optimum intervals between depot injections of either octreotide LAR and lanreotide for the suppression of serum GH and IGF-I in patients with acromegaly. Twenty-seven patients with acromegaly were randomly allocated to receive either three injections at 4 week intervals of octreotide LAR (n = 18) or five injections at 14 day intervals of lanreotide (n = 11); two patients participated in both arms. Prior to the first injection, at 4 and 6 weeks after the last injection of LAR, and at 10, 14 and 21 days after the last injection of lanreotide, serum mean GH and IGF-I levels were measured. RESULTS: In the LAR-treated group, at 4 and 6 weeks after the third injection 13 patients (72%) and 12 patients (67%), respectively, had a mean GH < 5 mU/l. IGF-I was normalized in 12 and 11 patients at these times. In the lanreotide-treated group, five (45%), four (36%) and three (27%) patients, respectively, had a GH < 5 mU/l at 10, 14 and 21 days after the last injection and eight, six and five patients had a normal serum IGF-I. CONCLUSION: There is marked variability in individual patient responses to depot somatostatin analogues. The establishment of optimal drug intervals requires careful assessment. For octreotide LAR many patients may be as adequately controlled with 6 weekly injections as with 4 weekly injections. It is important to measure serum GH profiles at intervals after initiating therapy with these drugs to individualize doses for each patient and hence minimize cost.

Acromegaly↗
PubMed2002

Acromegaly: evidence for a direct relation between disease activity and cardiac dysfunction in patients without ventricular hypertrophy.

BACKGROUND AND AIMS: Cardiac abnormalities, such as cardiomegaly and congestive heart failure, occur frequently in advanced acromegaly. Abnormalities of systolic and diastolic function, mostly associated with left ventricular (LV) hypertrophy, have been reported. The impact of disease activity on LV performance in patients with normal or slightly elevated LV muscle mass has not been demonstrated. PATIENTS AND METHODS: Conventional two-dimensional/Doppler echocardiography and tissue Doppler imaging (TDI) of the mitral annulus were performed in 13 patients with active acromegaly (AA) and normal or slightly elevated LV muscle mass (< 140 g/m2) and in 19 cured/well-controlled patients (CA). A group of 21 volunteers without symptoms or signs of cardiac disease served as controls (CON). The combined myocardial performance index (Tei-Index) was determined in all patients and controls. RESULTS: Muscle mass index of the left ventricle, ejection fraction, fractional shorting, E/ET-ratio, systolic (ST) and late diastolic (AT) annular velocities did not differ significantly between the three groups. In the AA group, the early diastolic annular velocity ET[7.13 +/- 2.11 (AA); 9.83 +/- 3.29 (CA); 10.10 +/- 1.70 m/s (CON); P < 0.05 AA vs. CA, P < 0.005 AA vs. CON] and the ET/AT-ratio [0.71 +/- 0.26 (AA); 0.95 +/- 0.33 (CA); 1.00 +/- 0.15 m/s (CON); P < 0.05 AA vs. CA, P < 0.005 AA vs. CON] were significantly reduced. Patients with AA had a longer deceleration time [209 +/- 19 (AA); 179 +/- 22 (CA); 185 +/- 26 ms (CON); P < 0.05]. The Tei-Index was significantly higher in AA in comparison with CON [0.50 +/- 0.15 (AA); 0.48 +/- 0.12 (CA); 0.41 +/- 0.10 (CON); P < 0.05 AA vs. CON]. Subjects with CA did not differ significantly from controls with respect to 2-D/Doppler echo- and TDI-derived parameters. CONCLUSION: The data demonstrate that diastolic dysfunction can be verified by tissue Doppler imaging in patients with active acromegaly with normal or slightly elevated muscle mass of the left ventricle and seems to be related to disease activity. The Tei-Index as a sensitive combined myocardial performance index can be used to complete the assessment of systolic and diastolic LV performance in acromegalic patients.

Acromegaly↗
PubMed2002

Thyroid vascularity is increased in patients with active acromegaly.

OBJECTIVE: To determine whether acromegalic patients have increased thyroidal vascularity and blood flow on colour flow Doppler sonography (CFDS). DESIGN: Prospective study of consecutive patients. PATIENTS: Twenty-four acromegalic patients (11 men, 13 women, age 49 +/- 9 years); 38 patients with nontoxic goitre (NTG; 12 men, 26 women, age 50 +/- 7 years); 36 normal subjects (controls; 16 men, 20 women, age 46 +/- 9 years). Among acromegalic patients, 10 had active, untreated disease (Acro-U), seven were in remission after surgery (Acro-R), seven had active disease under treatment with somatostatin analogues (SMSa) (Acro-SA) (Sandostatin LAR, 20 mg, every 28 days). MEASUREMENTS: CFDS pattern and intrathyroidal peak systolic velocity (PSV) were determined by a colour Doppler system with a 7.5-MHz linear transducer. PSV measurements were made at the level of the intrathyroidal arteries (normal values 3.8 +/- 1.0 cm/s). Thyroid volume was calculated by the ellipsoidal model. Assays included measurements of serum GH, IGF-I, free T4, free T3, TSH, antithyroglobulin (anti-Tg) and antithyroperoxidase (anti-TPO) antibodies, TSH-receptor antibodies (TRAb). RESULTS: Serum GH (+/- SD) and IGF-I (+/- SD) levels were: Acro-U: GH 26 +/- 31 microg/l, IGF-I 783 +/- 299 microg/l; Acro-SA: GH 15 +/- 25 microg/l, IGF-I 366 +/- 212 microg/l; Acro-R: GH 1.3 +/- 1.0 microg/l, IGF-I 241 +/- 99 microg/l. To convert values for serum GH to mU/l multiply by 2.6; to convert values for serum IGF-I to nmol/l multiply by 0.13075. All controls had CFDS pattern 0 (absent vascularity or minimal spots); among NTG patients, 36 had pattern 0 and two had pattern I (parenchymal blood flow with patchy uneven distribution). Five patients with acromegaly had pattern 0, 12 had pattern I and seven pattern II (mild increase of colour flow Doppler signal with patchy distribution). Among the five acromegalic patients with pattern 0, three were Acro-R and two were Acro-SA. Among patients with pattern I, six were Acro-U, two were Acro-SA and four were Acro-R. Among patients with pattern II, four were Acro-U and three Acro-SA; two patients of the latter group had elevated serum IGF-I under SMSa treatment. Intrathyroidal PSV was 3.8 +/- 1.0 cm/s in controls, 4.0 +/- 1.1 cm/s in NTG, 7.4 +/- 0.8 cm/s in Acro-U, 4.9 +/- 1.3 cm/s in Acro-SA treatment and 4.5 +/- 1.0 in Acro-R. (Acro-U vs. Acro-SA, P = 0.0003; vs. Acro-R, Controls, or NTG, P < 0.0001). PSV values in Acro-SA were higher than those observed in NTG or controls (P = 0.05, P = 0.01, respectively); PSV values in Acro-R did not differ from those in NTG or controls. Intrathyroidal PSV values were correlated with serum IGF-I (r = 0.73, P < 0.0001) and, although less strongly, GH levels (r = 0.54, P = 0.01). Goitre was present in 19 of 24 patients; diffuse in three and nodular in 16. Thyroid function was normal in all subgroups of acromegalic patients. Anti-Tg, anti-TPO antibodies and TRAb were negative in all subjects. CONCLUSIONS: Patients with active acromegaly have increased intrathyroidal blood flow (colour flow Doppler sonography pattern II, increased peak systolic velocity values); this was not observed in the large majority of patients under treatment with somatostatin analogues and in any patient in remission. Accordingly, colour flow Doppler sonography and peak systolic velocity measurements may be considered an additional useful peripheral parameter for rapid assessment of the activity of acromegaly.

Acromegaly↗
PubMed2003

Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly.

OBJECTIVE: Acromegaly has long been associated with increased mortality but few long-term follow-up data are available in patients treated for this disease. We therefore studied a group of 103 patients who underwent transsphenoidal adenomectomy for acromegaly between 1970 and 1999 and were followed for one to 30 years. DESIGN AND PATIENTS: A retrospective chart review was performed on 103 patients living in the province of Quebec, Canada. Mortality data were obtained by hospital charts, contact with the patient's family or death certificates. Stringent biochemical criteria were used to define remission (random GH < 2.5 microg/l, or GH nadir after an oral glucose load is < 1 microg/l and IGF-I within the normal range) and patient survival in the group in remission and the group with persistent disease were compared to survival of the population of Quebec, Canada, using the probabilities of the Poisson distribution. RESULTS: There were four deaths in the perioperative period, one of which was directly related to surgery. Initial remission was obtained in 82% of microadenomas, 60% of macroadenomas and 24% of invasive adenomas. The long-term (> or = 10 years) remission rate for surgery alone was 52%. A second transsphenoidal surgery, radiation therapy and/or octreotide were used in a subset of patients with persistent disease. Long-term remission was obtained in 63% of patients. Five (mean age, 64 years) of the 57 patients in remission died; this rate did not differ significantly from the mortality rate expected in the general population (P = 0.18). Thirteen (mean age, 59.8 years) of the 34 patients with persistent disease died; this rate was significantly higher than that expected in the general population (P = 0.008). CONCLUSIONS: Our observations confirm that uncontrolled acromegaly increases mortality compared to the general population and that mortality rates similar to the general population are restored once remission is induced.

Acromegaly↗
PubMed2003

Growth hormone, acromegaly, and heart failure: an intricate triangulation.

Short-term GH or IGF-I excess provides a model of physiological cardiac growth associated with functional advantage. The physiological nature of cardiac growth is accounted for by the following: (i) the increment in cardiomyocyte size occurs prevalently at expense of the short axis. This is the basis for the concentric pattern of left ventricular (LV) hypertrophy, with consequent fall in LV wall stress and functional improvement; (ii) cardiomyocyte growth is associated with improved contractility and relaxation, and a favourable energetic setting; (iii) the capillary density of the myocardial tissue is not affected; (iv) there is a balanced growth of cardiomyocytes and nonmyocyte elements, which accounts for the lack of interstitial fibrosis; (v) myocardial energetics and mechanics are not perturbed; and (vi) the growth response is not associated with the gene re-programming that characterizes pathologic cardiac hypertrophy and heart failure. Overall, the mechanisms activated by GH or IGF-I appear to be entirely different from those of chronic heart failure. Not to be neglected is also the fact that GH, through its nitric oxide (NO)-releasing action, contributes to the maintenance of normal vascular reactivity and peripheral vascular resistance. This particular kind of interaction of GH with the cardiovascular system accounts for: (i) the lack of cardiac impairment in short-term acromegaly; (ii) the beneficial effects of GH and IGF-I in various models of heart failure; (iii) the protective effect of GH and IGF-I against post-infarction ventricular remodelling; (iv) the reversal of endothelial dysfunction in patients with heart failure treated with GH; and (v) the cardiac abnormalities associated with GH deficiency and their correction after GH therapy. If it is clear that GH and IGF-I exert favourable effects on the heart in the short term, it is equally undeniable that GH excess with time causes pathologic cardiac hypertrophy and, if it is not corrected, eventually leads to cardiac failure. Why then, at one point in time in the natural history of acromegaly, does physiological cardiac growth become maladaptive and translate into heart failure? Before this transition takes places, the acromegalic heart shares very few features with other models of chronic heart failure. None of the mechanisms involved in the progression of heart failure is clearly operative in acromegaly, save for the presence of insulin-resistance and mild alterations of lipoproteins and clot factors. Is this enough to account for the development of heart failure? Probably not. On the other hand, it must be stressed that GH and IGF-I activate several mechanisms that play a protective role against the development of heart failure. These include ventricular unloading, deactivation of neurohormonal components, antiapoptotic effect and enhanced vascular reactivity. Ultimately, all data available concur to hypothesize that acromegalic cardiomyopathy represents a progressive model of cardiac hypertrophy in which the cardiotoxic and pro-remodelling effect is intrinsic to the excessive and unrestrained myocardial growth.

Acromegaly↗