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PubMedDate not supplied

[Acromegaly and sleep apnea syndrome (author's transl)].

Acromegaly associated with a Sleep Apnea Syndrome has but exceptionally been reported. Polygraphic recordings of sleep have been carried out in parallel with the determination of pituitary hormonal secretions, during the nycthemeral period before and after surgical treatment of the adenoma. There appears a Sleep Apnea Syndrome of the predominant obstructive type; the Apnea index is: 57 (N less than or equal to 4); the hypnogram is considerably jagged, with more than a thousand wakings and changes in the sleep stages, due to a great number of apneas. The deep slow sleep never occurs: no stages 3 and 4. The physiological peak of G.H. secreted in the beginning of the deep slow sleep thus does not appear in the Sleep Apnea Syndrome. The existence of a "false negative" criteria of a cured Acromegaly must be taken into consideration. The Sleep Apnea Syndrome must be differentiated from Narcolepsy and the usual Pickwickian syndrome. The Sleep Apnea Syndrome and Acromegaly seem to be two separate diseases, each one evolving independently. The cure of Acromegaly has not led to the cure of the Sleep Apnea Syndrome and the latter has not prevented the clinical and biological cure of Acromegaly. This may be an argument in favor of the independence of Acromegaly towards some hypothalamic structures.

Acromegaly↗
PubMedDate not supplied

[Galactorrhea and prolactin secretion in acromegaly].

Dependence of lactorrhea on the basic blood level of somatotropic hormone (STH), prolactin (PL), folliculostimulating hormone (FSH), and luteinizing hormone (LH) was studied in 62 patients with an active phase of acromegaly, untreated, and in 41 with inactive phase of the disease following radiation therapy. Thyrotropic hormone (TTH), PL, and STH secretion (basic and after intravenous injection of 200 micrograms of thyroliberin) was determined in 20 patients with active and in 6--with inactive acromegaly following radiation therapy. In patients with active acromegaly the percentage of lactorrhea in women constituted 60 and in men--9.5, and with inactive acromegaly (after radiation therapy) it was 13.3 and 0, respectively. Basic PL level was significantly elevated in both groups of patients. The principle role in the pathologenesis of lactorrhea in acromegaly proved to be played by increased PL secretion. Under the effect of thyroliberin PL secretion was significantly elevated in comparison with control in 15 patients with active acromegaly and in all cases at the stage of remission. Basic TTH level and this level after thyroliberlin stimulation was within the normal range. In 4 patients with lactorrhea the absence of TTH secretion was combined with unresponsiveness of PL secretion, this suggesting the presence of tumour growth. STH secretion was independent of lactorrhea both under basic conditions and after thyroliberin stimulation.

Acromegaly↗
PubMed1994

[Acromegaly and Graves-Basedow disease. Report of 3 cases].

Acromegaly is associated to thyroidal disorders such as hyperthyroidism. The Graves-Basedow disease as a cause of thyroid hyperfunction is very infrequent, with only 8 cases having been reported up to 1993. The authors present 3 patients with acromegaly who developed hyperthyroidism due to Graves-Basedow disease in the course of their disease. Two of the patients had acromegaly of 30 years of evolution and the third patient underwent consultation for clinical symptoms of hyperthyroidism with acromegaly being simultaneously diagnosed. All the patients had weight loss prior to diagnosis and the possibility of neoplasia associated to acromegaly was excluded. The hyperthyroidism responded well to initial treatment with antithyroid drugs in the three cases. The authors conclude that hyperthyroidism should be taken into consideration in the diagnosis of a patient with acromegaly and weight loss.

Acromegaly↗
PubMedDate not supplied

Combined octreotide and insulin therapy in acromegaly.

OBJECTIVE: To describe an unusual treatment strategy for certain patients with both acromegaly and insulin-requiring diabetes. METHODS: We present a case history of a man with a pituitary adenoma and diabetes mellitus and chronicle his response to various treatment modalities. RESULTS: Acromegaly, a disease state with excess growth hormone (GH) and insulin-like growth factor-I, is associated with carbohydrate intolerance. Octreotide, a somatostatin analogue, is used in the treatment of acromegaly to lower GH levels. Despite effective lowering of GH levels, certain patients with acromegaly have persistent or even worsening carbohydrate intolerance and may require insulin therapy. Such a regimen would necessitate five or more injections per day. We describe a 51-year-old man who was diagnosed with a GH-producing pituitary adenoma in 1987. Despite transsphenoidal resection, frontal craniotomy, and radiation therapy, symptoms and increased levels of GH persisted. The patient was diagnosed with diabetes mellitus in August 1989 and treated with glipizide. Because of persistently increased GH levels, he was treated with octreotide. His glycohemoglobin level increased to 21% despite use of maximal doses of glipizide. The patient refused insulin therapy because of his objection to numerous daily injections. Despite adjustments in diet and exercise, glycemic control remained poor. As a trial, we thus attempted combining octreotide and regular insulin in the same syringe and administering the medications in a single subcutaneous injection. No precipitate formation was evident, and he had no adverse effects. Glucose control improved, and the glycohemoglobin level was lower but still elevated. GH levels remained at less than 5 ng/mL. His symptoms of acromegaly were unchanged, but his overall attitude and energy level improved. CONCLUSION: The efficacy of the individual components of this treatment was demonstrated in the combination of insulin and octreotide. The combined administration of insulin and octreotide has limited application in patients with acromegaly and insulin-requiring diabetes mellitus.

Journal Article↗
PubMedDate not supplied

Central and peripheral neural responses in acromegaly.

OBJECTIVE: To assess the function of the central and peripheral nervous systems in patients with untreated acromegaly. METHODS: We recorded the somatosensory evoked potentials (SSEPs) and brain stem auditory evoked potentials (BAEPs) in 10 patients with untreated acromegaly of brief duration and in 20 age- and sex-matched healthy control subjects to evaluate the function of the central nervous system and at least the median and tibial components of the peripheral nerves. Electrophysiologic studies were done at the time of diagnosis and before the initiation of any treatment for acromegaly. We also studied the distal motor latency, nerve conduction velocity, compound muscle action potentials, and F response in the peroneal nerve; the sensory nerve conduction velocity and sensory potential amplitude were measured in the sural nerve. RESULTS: The mean duration of acromegaly (expressed as time elapsed since patients first recognized signs or symptoms) was 2.4 years. The N(9) and N(13) latencies in median SSEPs and the N(22) latency in tibial SSEPs were significantly prolonged in patients with acromegaly in comparison with the control group; however, central nervous system components of SSEPs and all components of BAEPs were normal. We also noted abnormalities in peroneal motor and sural sensory nerves. No correlation was found between the neurophysiologic data and the basal growth hormone level, the fasting blood glucose level, or the duration of disease. CONCLUSION: Our results suggest that peripheral, but not central, nervous system involvement exists in patients with untreated acromegaly of short duration.

Journal Article↗
PubMedDate not supplied

Acromegaly and non-Hodgkin's lymphoma.

OBJECTIVE: To present the fourth case report of development of a non-Hodgkin's lymphoma in a patient with active acromegaly. METHODS: We describe the clinical, laboratory, and imaging findings in a patient with untreated acromegaly in whom a large cell non-Hodgkin's lymphoma developed. RESULTS: Acromegaly is associated with several comorbid conditions. Among these is a higher incidence of several types of visceral malignant lesions, especially carcinoma of the colon. Growth hormone stimulates the hepatic production of somatomedins, such as insulin-like growth factors, which are known promoters of human growth and have also been implicated in tumorigenesis. In recent years, several cases of lymphoproliferative diseases have also been noted in patients with acromegaly. These conditions include multiple myeloma, lymphoma, and leukemia; three previous cases of non-Hodgkin's lymphoma have been described. In our patient, a 57-year-old man with acromegaly, magnetic resonance imaging of the pituitary gland disclosed a large intrasellar mass. Large cell non-Hodgkin's lymphoma was diagnosed. Six months of chemotherapy yielded complete remission. CONCLUSION: An additional case of non-Hodgkin's lymphoma in a patient with acromegaly supports the accumulating evidence of an increased risk for development of cancer in such patients.

Journal Article↗
PubMed2000

Prevalence of the sleep apnea syndrome in acromegaly population.

The prevalence of sleep apnea syndrome (SAS) in acromegaly is high. Consequences of SAS are serious and are associated with increased morbidity and mortality. The aim of this study was to assess the relative frequency and predictive factors for SAS in a group of patients with acromegaly (n=55). The presence of SAS was evaluated using the Polymesam device. Hormonal and clinical examination consisted of assessment of growth hormone, insulin-like growth factor I plasma levels, body mass index (BMI), neck circumference, age, sex, treatment modes of acromegaly and ear, nose and throat (ENT) examination. The relative frequency of SAS in our group of patients with acromegaly was 75%. Independent predictors of SAS were: increased activity of acromegaly, higher age and neck circumference. No association between SAS and BMI and ENT findings was observed. The role of gender was controversial.

Acromegaly↗
PubMed1997

Thyroid volume and function in patients with acromegaly living in iodine deficient areas.

The aim of our study was to evaluate the size and function of the thyroid in patients with acromegaly. In 39 patients concentrations of HGH, PRL, TSH, T3 and T4 were measured and the thyroid volume was calculated with the using of ultrasound examination. The control group comprised 5 patients with acromegaly in a stage of remission and 98 controls. We concluded that the size of the goiter in patients with acromegaly depends on serum concentration of HGH, but it does not depend on the concentration of TSH, T3, T4 and PRL. Goiter is present in 87% of patients with acromegaly, 46% of them are nodular goiters. The thyroid function in acromegaly is normal.

Acromegaly↗
PubMed1983

Hypothalamic-pituitary-thyroid axis in acromegaly.

To evaluate the hypothalamic-pituitary-thyroid axis in acromegaly, total and free thyroid hormones and TSH response to TRH were determined in 36 acromegalic patients. In 10 patients, rT3 and thyroxine binding globulin (TBG) were also assayed by radioimmunoassay. In 15 patients the TSH response to TRH was also studied after medical or surgical therapy of the acromegaly. In 34 patients total thyroid hormones were in the normal range whereas two patients had low serum levels of free thyroid hormones. Thirty-two of the acromegalic patients were euthyroid. However, only 43.7% of the euthyroid patients had a normal TSH response to TRH. Nine patients had a reduced TSH rise after TRH, whereas in 4 patients the response was exaggerated and 5 delayed. In all patients studied rT3 and TBG were in the normal range. After medical or surgical therapy of the acromegaly we observed improvement or normalization of the TSH response to TRH. In conclusion, the TSH response to TRH is frequently altered in acromegaly, whereas thyroid function is generally normal. Hypothalamic effects of GH hyperproduction may explain the alterations of TSH secretion in many cases in view of the normalization of TSH secretion after therapy of acromegaly.

Acromegaly↗
PubMed2003

Diagnosis and treatment of acromegaly complications.

The Pituitary Society in conjunction with the European Neuroendocrine Association held a consensus workshop to develop guidelines for diagnosis and treatment of the co-morbid complications of acromegaly. Fifty nine pituitary specialists (endocrinologists, neurosurgeons and cardiologists) assessed the current published literature on acromegaly complications in light of recent advances in maintaining tight therapeutic control of GH hypersecretion. The impact of elevated GH levels on cardiovascular disease, hypertension, diabetes, sleep apnea, colon polyps, bone disease, reproductive disorders, and neuropsychologic complications were considered. Guidelines are proposed for effective management of these complications in the context of overall acromegaly control. When appropriate, requirements for prospective evidence-based studies and surveillance database development are enunciated. Effective management of co-morbid acromegaly complications will lead to improved morbidity and mortality in acromegaly.

Acromegaly↗
PubMed1999

Serum IGF-I and IGFBP-3 levels for the assessment of disease activity of acromegaly.

To assess the disease activity of acromegaly in patients, we measured the changes in serum growth hormone (GH) levels during oral glucose tolerance test and the basal serum levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) in 29 acromegalic patients and 30 health persons served as normal controls. Based on the clinical and laboratory criteria, acromegaly was in an active state of disease in 18 patients and was inactive in the other 11 patients. Basal serum IGF-I levels were 177+/-116 ng/ml (mean+/-SD), 250+/-135 ng/ml and 810+/-297 ng/ml in the normal subjects, the inactive and active acromegalic patients, respectively. Basal serum IGFBP-3 levels were 1.71+/-1.29 microg/ml, 2.98+/-0.96 microg/ml and 6.82+/-1.31 microg/ml in the normal controls, the inactive and active acromegalic patients, respectively. Serum levels of IGF-I and IGFBP-3 significantly correlated with each other in the normal subjects as well as the patients. Both IGF-I and IGFBP-3 levels were significantly higher in the group of patients with active acromegaly than inactive acromegalic patients and the normal subjects but there was not statistically difference between the normal controls and the inactive acromegalics. While serum IGF-I levels presented considerable overlapping instances among the three groups, the serum IGFBP-3 of inactive patients and the normal controls could rarely reach 4.44 ng/ml, the lowest value of the active acromegalics. The serum IGF-I and IGFBP-3 levels declined with increased age in normal controls, but not in the patients with acromegaly. There was no sex predilection of serum IGF-I and IGFBP-3 found in our study. The results of this study indicated that the serum IGFBP-3 level is an important laboratory parameter for assessing growth hormone function in humans, and might be a more reliable discrimination for the disease activity of acromegaly than the serum IGF-I is.

Acromegaly↗
PubMed2003

Fracture risk is decreased in acromegaly--a potential beneficial effect of growth hormone.

Growth hormone (GH) is an anabolic hormone that may increase bone density and thus decrease fracture risk. Patients with acromegaly have an excess of GH, and we therefore investigated whether fracture risk was decreased in patients with acromegaly. We identified 206 patients newly diagnosed with acromegaly between 1983 and 1996 who underwent pituitary surgery. Each patient was compared with three age- and gender-matched controls randomly selected from the background population. Mean age at diagnosis was 46.0+/-12.6 years and 50% were women. Before diagnosis, six patients sustained six fractures during 2128 person years and after diagnosis six patients had ten fractures during 1282 years of follow-up. Among the controls, the corresponding figures were 23 subjects with 44 fractures during 6357 years of follow-up before diagnosis and 46 fractures in 28 subjects during 4051 person years. The fracture rate was significantly decreased before (incidence rate ratio: IRR=0.41, 95% CI: 0.18-0.93) but not after the diagnosis (IRR=0.69, 95% CI: 0.35-1.36) of acromegaly was made. Twenty-three patients had undergone measurements of bone mineral density by DXA after diagnosis, and their mean+/-SD Z-scores both in the lumbar spine (0.92+/-1.38) and femoral neck (0.54+/-1.02) were significantly higher than expected. A fracture before diagnosis was a significant risk factor for sustaining an incident fracture after diagnosis (RR=11.8, 95% CI: 4.7-29.3). In conclusion, fracture risk is significantly decreased in patients with acromegaly compared to controls probably due to an anabolic effect of growth hormone on bone.

Acromegaly↗
PubMed2006

Colorectal neoplasm and acromegaly.

The risk for colorectal carcinoma in acromegaly remains controversial. In our earlier study, we have demonstrated that the risk of colorectal carcinoma in Asian Indians with acromegaly is not increased and after this report, routine colonoscopy in our patients with acromegaly was abandoned. Subsequently, two consecutive young men aged 30 and 35, one 6 years after and other at the time of diagnosis of acromegaly had colorectal carcinoma respectively. None of them had family history of colonic neoplasm. These two younger patients with no other predisposition for colorectal neoplasm suggests that colonoscopy should be done in all patients with acromegaly at diagnosis and they should remain under surveillance.

Acromegaly↗
PubMed1979

Bone isoenzyme of serum alkaline phosphatase in acromegaly.

In 37 patients with active acromegaly and in 15 patients with inactive acromegaly, activity of bone isoenzyme of serum alkaline phosphatase correlated (P less than 0.001) with serum concentration of immunoreactive growth hormone. By using stepwise regression analysis, the predication of serum growth hormone values based on serum levels of bone isoenzyme of serum alkaline phosphatase, gamma-glutamyl transferase and calcium in these patients with acromegaly was within 1 S.D. range in 37 patients and in only 2 patients was it out of 2 S.D. range. By using discriminant analysis, based on bone and liver isoenzymes of serum alaline phosphatase and urinary hydroxyproline excretion, 87%, 60% and 97% of the classification of patients with active and inactive acromegaly and healthy adults, respectively, was correct. The multivariate approach offers a quantitative appraisal of the biochemical parameters of peripheral growth hormone action used as an indicator of growth hormone concentration in patients with acromegaly.

Acromegaly↗
PubMed1993

Contradictory clinical implications between paradoxical growth hormone responses to thyrotropin-releasing hormone and those to vasoactive intestinal peptide and luteinizing hormone-releasing hormone in acromegaly.

There is an almost general agreement on the clinical significance of TRH and bromocriptine (Br) tests in acromegaly. That is that positive GH responses to these tests (with an increase or a decrease, respectively) are known to be very frequently associated with the presence of PRL-containing somatotroph adenomas of the pituitary. In this context, however, very little is known about the clinical significance of paradoxical GH responses to vasoactive intestinal peptide (VIP) and LHRH in acromegaly. We therefore examined, as the principal objective of this study, whether a relationship exists among the GH (in some cases also PRL) responses to TRH, VIP, LHRH and Br in acromegaly. Another aim of this study was to examine whether a sexual difference exists in GH and PRL secretion in acromegaly. We examined a total of 24 patients comprising 8 men and 16 women. In agreement with previous reports, TRH-responders tended to have a higher level of basal PRL than TRH-nonresponders. In contrast, VIP-responders and LHRH-responders tended to have a lower PRL level than their respective counterparts. Although Br responsiveness was unexpectedly similar between TRH-responders and nonresponders, it was revealed that pure TRH-responders who were not responsive to VIP or LHRH were more sensitive to Br and more hyperprolactinemic than the remaining TRH-responders. This suggests that the simultaneous GH responsivity to VIP and/or LHRH in TRH-responders may be a factor which lowers their Br responsiveness and basal PRL levels. With respect to a sexual difference in GH and PRL secretion, it was revealed that female acromegalics had higher levels of basal GH and PRL than male patients. In addition, it was found that female acromegalics had supernormal levels of basal PRL, but a subnormal PRL responsiveness to TRH. As the major implication of this study, we hypothesize that the positive GH response to TRH associated with a high sensitivity to Br may, as already suggested, be characteristic of PRL-containing somatotroph adenomas, whereas the GH responsivity to VIP, and possibly also to LHRH, co-existing with no or low sensitivity to Br may be a feature of pure somatotroph adenomas. Although this study is devoid of immunohistochemical evidence to support this hypothesis, we suggest that the present in vivo data may be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testings in acromegaly.

Acromegaly↗
PubMed1995

Clinical significance of the growth hormone response to vasoactive intestinal peptide and gonadotropin-releasing hormone in acromegaly.

GH-secreting pituitary adenomas causing acromegaly can be classified into at least two types, i.e. the lactotroph-like adenoma and somatotroph-like adenoma. From a functional point of view, the lactotroph-like adenoma is characterized by positive GH responses to TRH and bromocriptine (Br) with a GH increase or decrease, respectively, whereas the somatotroph-like adenoma is characterized by a high GH response to GHRH and a low GH response to TRH and Br. In this study, we examined whether the loading of vasoactive intestinal peptide (VIP) and GnRH, another hypothalamic hormone capable of stimulating GH secretion in acromegaly, have a pathophysiological significance as TRH, GHRH, and Br tests. In 52 patients with active acromegaly, we performed iv bolus injections of TRH (500 micrograms), GHRH (100 micrograms), VIP (100 micrograms), and GnRH (100 micrograms), and a peroral administration of Br (2.5 mg), in order to compare the GH responses to these loads. There was a significant correlation that the higher was the GH response after TRH the greater was the GH decrease after Br. Although statistically insignificant, there was a trend (0.05 < p < 0.1) that the higher was the GH response after GHRH the smaller was the GH decrease after Br. In addition, as novel findings, we observed that the GH responses to GHRH, VIP, and GnRH were in significant positive correlations to each other, and that the higher were the GH responses after VIP and GnRH the smaller was the GH decrease after Br. In agreement with this, we also found that a simultaneous GH responsivity to VIP and/or GnRH in TRH-responsive acromegalics significantly enhanced the GH response to GHRH and lowered the Br responsiveness compared to the data of pure TRH-responders. From these results, we hypothesize that the positive GH responsiveness to VIP and GnRH, like that to GHRH, may be a feature of the somatotroph-like pituitary adenoma causing acromegaly. The present results appear to be of some help in understanding the basis of the great variabilities in the GH responses to various dynamic testings in acromegaly.

Acromegaly↗
PubMed2006

Serum insulin-like growth factor-I measurement in the follow-up of treated acromegaly: comparison of four immunoassays.

BACKGROUND: Measurement of serum insulin-like growth factor I (IGF-I) is currently used for the diagnosis and for monitoring treated acromegaly. In this work, we have studied the performances of four IGF-1 immunoassays in the follow-up of acromegaly. METHODS: The study was carried out on 52 sera from 40 patients with treated acromegaly. Serum IGF-I was measured with radioimmunoassays from Immunotech, DiaSorin and Schering Laboratories and by the chemiluminescent automated immunoassay (Advantage) from Nichols. Normal age- and gender-matched subjects constituted the reference population for two assays. RESULTS: Deming regression and Bland-Altman analyses showed a high correlation with the four methods tested. The use of restricted number of age-adjusted controls with the Immunotech assay, the DiaSorin assay and the Schering assay induced discordance with the Nichols assay in the interpretation of results in treated acromegaly. When normal ranges of the Immunotech assay and the DiaSorin assay were defined from large number of controls, the frequency of normal IGF-I became similar as that obtained with the Nichols assay. CONCLUSION: The four immunoassays display suitable analytical performance for serum IGF-I measurement in the follow-up of acromegaly. For correct interpretation, IGF-I normal ranges should be defined in a large number of age-adjusted healthy subjects.

Acromegaly↗
PubMed2002

High output heart failure in patients with newly diagnosed acromegaly.

PURPOSE: We sought to determine the prevalence and characteristics of heart failure in patients with newly diagnosed acromegaly. SUBJECTS AND METHODS: We assessed 102 consecutive patients who had acromegaly (44 men; age range, 22 to 71 years) for signs and symptoms of heart failure. We included a control group of 33 nonobese healthy subjects (13 men; age range, 26 to 70 years). Cardiac morphologic parameters, left ventricular mass index, ejection fraction, end-systolic wall stress, and cardiac index were measured by echocardiography. Endocrinological assessment was performed in all participants. RESULTS: Of the 102 patients, 10 (10%) had overt heart failure at the time of diagnosis of acromegaly, 9 of whom were men (P <0.01). Patients with acromegaly and heart failure had an increased mean (+/- SD) left ventricular end-diastolic diameter (76 +/- 11 mm) compared with those without heart failure (53 +/- 6 mm, P <0.001) and control subjects (49 +/- 5 mm, P <0.001). Patients with heart failure had higher left ventricular mass index (230 +/- 56 g/m2 vs. 118 +/- 40 g/m(2), P <0.001) and end-systolic wall stress (237 +/- 79 x 10(3) dyn/cm2 vs. 111 +/- 42 x 10(3) dyn/cm2, P <0.001), but lower ejection fraction (42% +/- 17% vs. 66% +/- 9%, P <0.001), in comparison with patients without heart failure. The mean cardiac index was significantly higher in patients with heart failure (4.3 +/- 1.8 L/min-m2) than in those without heart failure (3.5 +/- 0.8 L/min-m2, P = 0.04) or in control subjects (3.1 +/- 0.6 L/min-m2, P = 0.002). Two factors were independently associated with heart failure in acromegalic patients: cardiac index (odds ratio [OR] per SD of 1.0 L/min-m2 = 16; 95% confidence interval [CI]: 1.8 to 135) and ejection fraction (OR per SD of 12% = 0.7; 95% CI: 0.6 to 0.9). CONCLUSION: High output heart failure with a modest decline in ejection fraction is frequently detected at the time of diagnosis of acromegaly. Left ventricular hypertrophy in these patients is characterized by a dilated ventricle and an increased left ventricular mass that is primarily due to the enlarged chamber diameter.

Acromegaly↗