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Biomedical subjects

Philippe Chanson

Publications and source records attributed to Philippe Chanson.

At least 19 recordsLinked to original sources
PubMed2006

Cardiac effects of growth hormone treatment in chronic heart failure: A meta-analysis.

CONTEXT: Experimental studies suggest that GH treatment may improve cardiovascular parameters in chronic heart failure (CHF). However, clinical trials involved small numbers of patients and did not allow a conclusion to be drawn on the effect of this treatment in humans. OBJECTIVE: We systematically reviewed and analyzed all randomized controlled trials and open studies of sustained GH treatment in CHF. STUDY SELECTION: Twelve trials were identified in three databases. We conducted a combined analysis of GH effects on cardiovascular parameters using the overall effect size to evaluate significance and computing the weighted mean differences with and without treatment to assess effect size. DATA SYNTHESIS: GH treatment significantly modified morphological cardiovascular parameters [interventricular septum thickness, +0.55 (sd, 0.43) mm (P < 0.001); posterior wall thickness, +1.01 (0.44) mm (P < 0.01); left ventricle (LV) end-diastolic diameter, -2.02 (1.22) mm (P < 0.01); and LV end-systolic diameter, -5.30 (2.33) mm (P < 0.05)]; LV and systemic hemodynamics [LV end-systolic wall stress, -38.9 (13.3) dynes/cm(2) (P < 0.001); LV ejection fraction, +5.10 (1.74)% (P < 0.05); and systemic vascular resistance, +195.0 (204.5) dyn x sec(-1) x cm(-5) (P < 0.01)]; and functional parameters [New York Heart Association class, -0.97 (0.23) (P < 0.01); exercise duration, +103.7 (37.6) sec (P < 0.001); and maximal oxygen uptake, +2.48 (1.76) ml/kg x min (P < 0.01)]. Subgroup analysis and meta-regression showed significant relationships between the IGF-I response and GH treatment effects. CONCLUSION: Our meta-analysis suggests that GH treatment improves several relevant cardiovascular parameters in patients with CHF. However, these results must be confirmed by a large randomized placebo-controlled trial on hemodynamic, morphological, and functional parameters during long-term high-dose GH treatment of patients with CHF.

Growth Hormone↗
PubMed2006

McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients.

BACKGROUND: Acromegaly, which may be present in patients with McCune-Albright syndrome (MCAS), in association with café-au-lait spots, precocious puberty, and fibrous dysplasia, is often difficult to treat surgically because skull base bone dysplasia prevents the removal of the pituitary adenoma. Somatostatin analogs (SAs) generally give only partial responses. The use of radiotherapy (RT) is controversial because of a possible risk of bone sarcomatous transformation. AIM: This study was a retrospective analysis of the efficacy and adverse effects of different treatment modalities in six patients with both MCAS and acromegaly. PATIENTS AND METHODS: Because surgery was impossible and SA failed to normalize GH/IGF-I hypersecretion, five of the six patients received fractionated RT (45-55 Grays). Three patients (two with previous RT) were also prescribed pegvisomant. We analyzed the clinical features of acromegaly, GH, and IGF-I concentrations and bone radiological features. RESULTS: GH and IGF-I concentrations fell after RT (median follow-up, 5 yr; range, 0.5-9 yr). Symptoms of acromegaly improved in parallel. Bone sarcomatous transformation was only noted in one patient in a region (the mandible) outside the radiation field. RT alone and/or combined with SA failed to normalize GH/IGF-I levels in the five patients concerned. In contrast, IGF-I levels normalized very rapidly (5-9 months) in the three patients receiving pegvisomant (10-20 mg/d). CONCLUSION: RT may be an option for the treatment of acromegaly in patients with MCAS when surgery is impossible and SA therapy is ineffective. However, although no bone sarcomatous transformation was observed within the radiation field in this series, this risk cannot be ruled out. As shown in this small series of severely affected patients, pegvisomant therapy may thus be useful to normalize IGF-I levels rapidly.

Acromegaly↗
PubMed2006

A PRKAR1A mutation associated with primary pigmented nodular adrenocortical disease in 12 kindreds.

CONTEXT: Primary pigmented nodular adrenocortical disease (PPNAD), a rare cause of corticotropin-independent Cushing syndrome, can be part of Carney complex (CNC), an autosomal dominant multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac myxomas, and endocrine tumors or be isolated (i). Germline PRKAR1A-inactivating mutations have been observed in both CNC and iPPNAD, but with no apparent genotype-phenotype correlation. OBJECTIVE: The objectives of the study were a detailed phenotyping for CNC manifestations in 12 kindreds bearing the same PRKAR1A mutation and a study of the consequences of the mutation and a potential founder effect. DESIGN: The study consisted of descriptive case reports. SETTING: The study was conducted at two referral centers. PATIENTS: The patients described in this study were referred for PRKAR1A gene mutation analysis because of a diagnosis of apparently iPPNAD. RESULTS: We describe a 6-bp polypyrimidine tract deletion [exon 7 IVS del (-7-->-2)] in 12 unrelated kindreds that were referred for Cushing syndrome due to PPNAD. Nine of the patients had no family history; in two, there was a family history of iPPNAD. Only one patient met the criteria for CNC. Relatives carrying the same mutation had no manifestations of CNC or PPNAD, suggesting a low penetrance of this PRKAR1A defect. A founder effect was excluded by extensive genotyping of chromosome 17 markers. CONCLUSIONS: In conclusion, a small intronic deletion of the PRKAR1A gene is a low-penetrance cause of mainly iPPNAD; it is the first PRKAR1A genetic defect to have an association with a specific phenotype.

Adolescent↗
PubMed2006

Pituitary tumour transforming gene (PTTG) expression correlates with the proliferative activity and recurrence status of pituitary adenomas: a clinical and immunohistochemical study.

BACKGROUND: The pituitary tumour transforming gene (pttg) plays a central role in pituitary tumorigenesis, but PTTG protein expression is poorly documented and its relationship with tumour cell proliferation and the prognosis of pituitary adenomas is unclear. AIM: The aim of this study was to evaluate the immunohistochemical expression of PTTG and Ki-67 in 45 human pituitary adenomas according to the tumour histotype, aggressiveness and persistence/recurrence status. PATIENTS AND METHODS: The tumours comprised 37 macroadenomas and 8 microadenomas. Twenty patients experienced disease persistence or recurrence after transsphenoidal surgery. Disease recurrence was observed in 16 patients, 8-72 months after surgery. RESULTS: No PTTG or Ki-67 expression was detected in normal pituitary tissue. In pituitary adenomas, tumour nuclei were positive for PTTG and Ki-67 in 89 and 98% of samples, respectively, and there was a strong correlation between the expression of the two proteins (P < 0.001). By the ROC curves method, a PTTG score of 3.3% was the best cut-off for distinguishing between recurrent and nonrecurrent pituitary adenomas (P < 0.05; sensitivity 60%; specificity 76%). A 2.9% cut-off was obtained for both PTTG (P < 0.01; sensitivity 77%; specificity 71%) and Ki-67 (P < 0.05; sensitivity 85%; specificity 64%) among patients with more than 1 year of follow-up. Neither PTTG nor Ki-67 expression was influenced by the maximal tumour diameter, tumour grade, age, gender or presurgical medical treatment. Both PTTG and Ki-67 tumour score > 2.9% identified a subgroup of patients with a significantly higher recurrence-free interval (P < 0.01). By multivariate analysis, a > 2.9% Ki-67 tumour score was the best predictor of pituitary tumour persistence/recurrence after surgery (chi(2) = 8.2, P < 0.01). CONCLUSION: PTTG is expressed in approximately 90% of pituitary tumours of different histotypes but with a high variability from one case to another. As expected, PTTG expression parallels that of Ki-67 and both are correlated to a more aggressive behaviour. However, a 2.9% Ki-67 cut-off proved to be the most reliable biological marker for predicting the recurrence potential of these tumours, when an adequate postsurgical follow-up is considered.

Adenoma↗
PubMed2005

Comparison of fast Fourier transform and autoregressive spectral analysis for the study of heart rate variability in diabetic patients.

INTRODUCTION: Impaired heart rate variability (HRV) is associated with poor outcome in diabetic patients. The present prospective study compared spectral components of HRV obtained by either fast Fourier transform (FFT) or autoregressive (AR) analyses in diabetic patients. METHODS: Thirty patients (49+/-12 years; 11 F/19 M; 60% with insulin-dependent type 1 diabetes) underwent 24-h ambulatory electrocardiographic recordings which comprised a 10-min resting period at the onset (n=30) and end (n=12) of the monitoring. Spectral analysis was applied to 5-min sequences at rest, and the total power and power spectra integrated over the very low (VLF), low (LF), and high (HF) frequency bands were obtained. RESULTS: Fifteen patients had moderately depressed HRV and two patients had highly depressed HRV (standard deviation of the RR intervals over 24-h<100 ms and <50 ms, respectively). Both raw data and ln-transformed data were significantly different between FFT and AR. All spectra component were obtained in each patient using FFT. Using AR, the LF/HF ratio could not be estimated or was zero in 4 and 11 patients, respectively. The AR results were more sensitive than FFT results to minor changes (+/-5%) in the timing of the onset of analysis. The day-to-day reproducibility of FFT was better than that of AR. Finally, using FFT, the LF/HF ratio, LFnu, and HFnu were essentially redundant (nu=normalized units). CONCLUSIONS: The spectral components of short-term HRV calculated by using the FFT and AR methods were not interchangeable and FFT analysis must be preferred in diabetic patients.

Adult↗
PubMed2005

Outcome of gamma knife radiosurgery in 82 patients with acromegaly: correlation with initial hypersecretion.

CONTEXT: Because surgical and medical therapies of acromegaly all have specific limitations, radiotherapy has been used as an adjunctive strategy. Stereotactic radiosurgery has not yet been widely evaluated. OBJECTIVE: The objective was to perform an analysis of long-term hormonal effects and tolerance of gamma knife radiosurgery. DESIGN: Eighty-two patients were prospectively studied over a decade, with a mean follow-up of 49.5 months. SETTING: All patients were treated at the Department of Functional Neurosurgery of Marseille, France. PATIENTS: The patients included 82 with active acromegaly, of whom 63 had previous transsphenoidal surgery. INTERVENTION: Intervention included radiosurgery using the Leksell Gamma Unit B model. MAIN OUTCOME MEASURES: Remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (at least 3 months). RESULTS: Seventeen percent of the patients were in remission without any treatment. Twenty-three percent previously uncontrolled on somatostatin agonists fulfilled the same criteria after gamma knife while maintained on medical treatment. Initial GH and IGF-I levels off somatostatin agonists were significantly higher in uncured than in remission group (P = 0.01 and 0.047, respectively). Withdrawal of somatostatin agonists at the time of radiosurgery had no incidence on the outcome. No significant difference was found in success rate whether patients had previously been treated or not. Long-term side effects included complete (n = 2) or partial (n = 12) hypopituitarism diagnosed 1-7 yr after gamma knife. CONCLUSIONS: Gamma knife radiosurgery may represent a therapeutic approach in patients with moderate initial or residual GH hypersecretion.

Acromegaly↗
PubMed2005

A critical analysis of pituitary tumor shrinkage during primary medical therapy in acromegaly.

CONTEXT: Somatostatin analogs have been successfully used to treat patients with GH-secreting pituitary adenomas because they are safe, effective, and usually well tolerated. The results of studies evaluating acromegaly treatment with the somatostatin receptor ligands (SRLs), octreotide and lanreotide, have supported the use of these agents for primary medical therapy before or as an alternative to traditional interventions of surgery and radiotherapy in selected cases. EVIDENCE ACQUISITION: We therefore undertook a systematic literature overview to characterize the results of studies involving primary therapy with somatostatin analogs and their effects on pituitary tumor size. Because most studies in which pituitary tumor shrinkage has been assessed involve uncontrolled, open-label, prospective trials or retrospective case series, the lack of a control arm does not permit pooling of data in a metaanalytic fashion to determine tumor size reduction. Therefore, this systematic review was designed to document and stratify data by study design, summarize therapeutic regimens and patient characteristics, assess the percentage of patients showing changes in tumor size, and calculate the weighted average effect on size reduction. EVIDENCE SYNTHESIS: Overall, for patients who experience significant shrinkage, an approximately 50% decrease in pituitary mass is achieved when a somatostatin analog is used exclusively or before surgery or radiotherapy. Fourteen studies (n = 424) provided a definition of significant tumor shrinkage, and the results showed that 36.6% (weighted mean percentage) of patients receiving primary SRL therapy for acromegaly experienced a significant reduction in tumor size. The weighted mean percent reduction in tumor size was 19.4% for those studies in which all patients received SRLs and change in tumor size was reported for all patients. CONCLUSIONS: Clinical implications are discussed for patients in whom tumor size control with SRLs is an important objective, typically those who have failed surgery or are being treated with primary medical therapy with large tumors.

Acromegaly↗
PubMed2005

[Historical perspective of hormone replacement therapy].

Clinical manifestations of menopause are partly related to estrogen deficiency. Estrogen replacement was long believed to reverse not only climacteric symptoms but also other chronic conditions associated with menopause such as osteoporosis, cognitive disorders or cardiovascular risk. However, it rapidly became obvious that hormone replacement therapy (HRT) was also associated with an increased risk of breast cancer and venous thrombo-embolic events. Until the end of the 1990's, based on cohort studies, HRT was thought to prevent cardiovascular complications of atherosclerosis. Risk/benefit ratio was thus considered as in favor of HRT, explaining its very wide prescription, after specific contra-indications have been ruled out. In 1998, the publication of HERS, the first randomized controlled study evaluating the effects of HRT in secondary cardiovascular prevention, allowed the scientific community to be conscious of the fact that HRT, not only did not prevent cardiovascular risk but also, probably, aggravated it. In 2002, the premature interruption of WHI study, by confirming that this was also true for primary prevention, has profoundly altered the common beliefs about HRT. Indeed, if HRT was associated with an increased cardiovascular risk, the benefits/risks ratio became unfavorable. Since that time, less women are treated and some of them have stopped their HRT. Recent recommendations have been published about indications of HRT, mainly based on the presence of climacteric symptoms. The potential interest of transdermic route for administration of estrogens needs to be confirmed. The potential deleterious effect of progestins needs to be explored. The difficult story of HRT had, at least, the merit to show, one more time, that in medicine, scientific evidence is always better than beliefs.

Aged↗
PubMed2005

Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs.

INTRODUCTION: Invasive GH-secreting pituitary adenomas are rarely cured by surgery and although long-term therapy with somatostatin analogs (SSAs) may be employed, hormonal control is achieved in only 60% of cases. The impact of tumor debulking on subsequent control of acromegaly with SSAs has not been studied previously. METHODS: We studied retrospectively the response to SSA therapy in acromegalic patients before and after incomplete surgical tumor excision. A case review identified 24 acromegalic patients who had received SSA therapy for > or = 1 month before and after gross total resection or debulking of adenomas. No patient received radiotherapy or combination treatment with SSAs and dopamine agonists during the study. GH and IGV-I responses to SSAs were recorded pre- and postoperatively. Postoperative SSA therapy was begun after a washout period of 1-3 months to assess the hormonal effects of the surgery alone. RESULTS: Before preoperative SSA treatment, 24/24 (100%) patients had elevated GH levels and IGF-I levels were elevated in 19/21 (90.5%) patients with recorded values. During preoperative SSA treatment, GH and IGF-I levels were normalized in 7/24 (29.2%) and 11/24 (45.8%) patients respectively. Following postoperative washout, GH was controlled in only 3/24 (12.5%) patients, while IGF-I was controlled in 8/19 (42.1%) patients with available data. During the second SSA treatment period, normal GH levels were seen in 13/24 (54.2%) patients, while IGF-I control was noted in 18/23 (78.3%). CONCLUSION: Gross total tumor resection or debulking increases the likelihood of achieving biochemical disease control with SSAs in acromegalic patients with adenomas that were not amenable to complete surgical resection and in whom primary SSA therapy was unable to achieve good biochemical control.

Acromegaly↗
PubMed2005

Type A insulin resistance syndrome revealing a novel lamin A mutation.

Particular forms of polycystic ovary syndrome with severe hyperandrogenism, acanthosis nigricans, and marked insulin resistance, defining the type A insulin resistance syndrome, are due to insulin receptor gene mutations. However, the majority of affected individuals do not have such mutation, arguing for the genetic heterogeneity of this syndrome. The familial partial lipodystrophy of the Dunnigan type, one of the diseases due to mutations in the lamin A/C (LMNA) gene, is characterized by a lipodystrophic phenotype and shares some clinical and metabolic features with the type A syndrome. We describe here the case of a nonobese 24-year-old woman affected with type A syndrome without clinical lipodystrophy. We linked this phenotype to a novel heterozygous missense mutation in the LMNA, predicting a G602S amino acid substitution in lamin A. This mutation cosegregated with impaired glucose tolerance, insulin resistance, and acanthosis nigricans in the absence of clinical lipodystrophy in the family. The skin fibroblasts from the proband exhibited nuclear alterations similar to those described in other laminopathies, and showed several defects in the insulin transduction pathway. This study further extends the vast range of diseases linked to LMNA mutations and identifies another genetic cause for the type A insulin resistance syndrome.

Adult↗
PubMed2004

Testicular anti-mullerian hormone secretion is stimulated by recombinant human FSH in patients with congenital hypogonadotropic hypogonadism.

Serum anti-Mullerian hormone (AMH), a prepubertal Sertoli cell marker, declines during puberty as an early sign of testicular testosterone (T) production. When T synthesis or action is impaired, serum AMH is abnormally high in the first months after birth and at puberty but normal between these two periods. We postulated that FSH might be responsible for AMH up-regulation in the absence of androgen inhibition. To test this hypothesis, we administered recombinant human (rh) FSH to eight patients aged from 18-31 yr with untreated congenital hypogonadotropic hypogonadism. This situation is ideal to study the effect of FSH on AMH production because it avoids interference by endogenous gonadotropins and T. The patients received daily sc injections of 150 IU rhFSH for 1 month, followed in seven of them by a combined treatment of rhFSH plus human chorionic gonadotropin (hCG; 1500 UI im, twice a week) for 2 months. Gonadotropins, T, AMH, and inhibin B were measured in plasma before treatment every 10 d during rhFSH treatment and every month during combined rhFSH and hCG treatments. All hormones were at prepubertal levels before treatment. Although LH and T did not vary, AMH and inhibin B levels gradually increased after 20 d of FSH administration. However, in contrast to rhFSH alone, the combined rhFSH plus hCG stimulation of the testis dramatically suppresses the secretion of AMH and induced a modest but significant reduction of circulating inhibin B levels. We conclude that FSH stimulates AMH production in the testis when it is at a prepubertal stage. In addition, the decrease of serum AMH during combined rhFSH and hCG testicular stimulation is in agreement with the concept that during pubertal development and in adult life, the suppressive effect of LH-driven testicular androgens outweighs the stimulating effect of FSH on AMH production by Sertoli cells. Finally, the hCG-induced decrease in inhibin B suggests that in humans, as previously demonstrated in monkeys, testicular T is also able to inhibit inhibin B secretion.

Adolescent↗
PubMed2004

Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials.

Patients with hypopituitarism have an increased risk of cardiovascular mortality. GH treatment could modify the cardiovascular risk in adults with GH deficiency, but most published clinical trials involved few patients and the results are variable. We conducted a systematic review of blinded, randomized, placebo-controlled trials of GH treatment in adult patients with GH deficiency published up to August 2003. Thirty-seven trials were identified. We combined the results for effects on lean and fat body mass; body mass index; triglyceride and cholesterol [high-density lipoprotein, low-density lipoprotein (LDL), and total] levels; blood pressure; glycemia; and insulinemia. Overall effect size was used to evaluate significance, and weighted differences between GH and placebo were used to appreciate the size of the effect. GH treatment significantly reduced LDL cholesterol [-0.5 (SD 0.3) mmol/liter], total cholesterol [-0.3 (0.3) mmol/liter], fat mass [-3.1 (3.3) kg], and diastolic blood pressure [-1.8 (3.8) mm Hg] and significantly increased lean body mass [+2.7 (2.6) kg], fasting plasma glucose [+0.2 (0.1) mmol/liter], and insulin [+8.7 (7.0) pmol/liter]. All effect sizes remained significant in trials with low doses and long-duration GH treatment. Thus, GH treatment has beneficial effects on lean and fat body mass, total and LDL cholesterol levels, and diastolic blood pressure but reduces insulin sensitivity. The global cardiovascular benefit remains to be determined in large trials with appropriate clinical endpoints.

Adult↗
PubMed2004

Pituitary magnetic resonance imaging findings do not influence surgical outcome in adrenocorticotropin-secreting microadenomas.

The pituitary origin of ACTH secretion in ACTH-dependent hypercortisolism can be difficult to assess, as magnetic resonance imaging (MRI) frequently fails to identify ACTH-secreting microadenomas or, on the contrary, may give false positive images of microadenomas. The choice of therapeutic option for patients with such normal MRI findings is controversial. Some groups propose routinely pituitary surgery, whereas others consider that neurosurgical exploration may be less successful and more harmful, and therefore prefer other types of management. The aim of this study was to compare surgical outcomes between patients with Cushing's disease (CD) and normal vs. positive pituitary MRI findings. Fifty-four patients (44 women and 10 men) with CD, operated on after 1996 in two centers (Kremlin-Bicêtre and Bordeaux) and followed postoperatively during a mean period of 19.9 +/- 22.7 months (range, 1-89 months), were enrolled in this retrospective study. Twenty-eight patients had normal pituitary MRI findings, and the pituitary origin of ACTH was established by bilateral petrosal sinus sampling in all of these cases. Twenty-six patients had positive MRI findings clearly showing a microadenoma. The two groups were not significantly different in terms of the sex ratio, age, frequency of hypertension, or diabetes, basal 24-h urinary free cortisol levels and follow-up. All of the patients were operated on by two experienced neurosurgeons using the same surgical protocol. Selective adenomectomy was performed when a tumor was identified, and subtotal hypophysectomy was performed when the lesion was uncertain or when no tumor was found during surgical exploration. Respectively, 50% and 84% of patients with normal and positive MRI results underwent adenomectomy (P < 0.05). A pituitary adenoma (confirmed by pathological examination) was found at surgery in 53% and 88% of patients in the normal and positive MRI groups, respectively (P < 0.05). The early surgical success rate (combining patients with corticotropic deficiency and patients with eucortisolism) was similar in the normal and positive MRI groups (78% and 88%, respectively; P = 0.85). The recurrence rate was lower in the normal MRI group, but the difference did not reach statistical significance (9% vs. 30%; P = 0.07). The final remission rate at the last visit was similar in the normal and positive MRI groups (72% and 61%, respectively; P = 0.29). Postoperative complications were also similar: 10 patients (36%) with normal MRI and five patients (20%) with positive MRI had at least one postoperative complication (surgical and/or pituitary deficiency; P = 0.12). Thus, the outcome of pituitary surgery in CD appears to be similar regardless of whether pituitary MRI shows a microadenoma. We recommend neurosurgical pituitary exploration as the first-line treatment of CD, provided that the pituitary origin of ACTH secretion is confirmed by bilateral petrosal sinus sampling in patients with normal pituitary MRI findings.

Adenoma↗
PubMed2004

Parental origin of Gsalpha mutations in the McCune-Albright syndrome and in isolated endocrine tumors.

Activating mutations of the Gsalpha gene are detected in different endocrine tumors, such as GH-secreting adenomas and toxic thyroid adenomas, and in hyperfunctioning glands from patients with McCune-Albright syndrome (MAS). There is increasing evidence that the Gsalpha gene is subjected to imprinting control and that Gsalpha imprinting plays a key role in the pathogenesis of different human diseases. The aim of this study was to investigate the presence of a parent specificity of Gsalpha mutations in 10 patients affected with MAS and 12 isolated tumors (10 GH-secreting adenomas, one toxic thyroid adenoma, and one hyperfunctioning adrenal adenoma). The parental origin of Gsalpha mutations was assessed by evaluating NESP55 and exon 1A transcripts, which are monoallelically expressed from the maternal and paternal alleles, respectively. By this approach, we demonstrated that in isolated GH-secreting adenomas, as well as in MAS patients with acromegaly, Gsalpha mutations were on the maternal allele. By contrast, the involvement of other endocrine organs in MAS patients was not associated with a particular parent specificity, as precocious puberty and hyperthyroidism were present in patients with mutations on either the maternal or the paternal allele. Moreover, isolated hyperfunctioning thyroid and adrenal adenomas displayed the mutation on the maternal and paternal alleles, respectively. These data confirm the importance of Gsalpha imprinting in the pituitary gland and point out the high degree of tissue specificity of this phenomenon.

Adenoma↗
PubMed2004

Long-term outcome of patients with acromegaly and congestive heart failure.

Cardiovascular complications are a major cause of morbidity and mortality in patients with acromegaly. Normalization of GH secretion is associated with an improvement in structural and functional cardiac abnormalities. However, the long-term cardiac effects of treatment for acromegaly have not been studied in patients who have already developed chronic congestive heart failure (CHF). We reviewed the charts of 330 consecutive patients with acromegaly treated in two French and Belgian centers since 1985. Ten patients with both acromegaly and CHF (eight men, two women, mean age 49.7 yr) were studied retrospectively. One of them was excluded because CHF was due to severe aortic stenosis.CHF (New York Heart Association stages III-IV and echocardiography showing dilated hypokinetic cardiomyopathy with left ventricular systolic dysfunction and a left ventricular ejection fraction less than 45%) was diagnosed before, concomitantly, or after acromegaly in, respectively, two, five, and two patients. Three patients were referred with terminal heart failure requiring transplantation.One patient had transient CHF associated with a hypertensive crisis. The other eight patients had symptomatic chronic CHF. Control of GH hypersecretion failed, totally or partially, in three patients: one had a long-term survival, and the two others died at 1 and 5 yr. Good GH control was achieved in five patients: four of these are still alive 2-16 yr after diagnosis of CHF, their clinical status is stable or improved, and their quality of life is good. Overall, the 1- and 5-yr mortality (or transplantation) rates for patients with chronic symptomatic CHF were 25% (2 of 8 patients) and 37.5% (3 of 8 patients), respectively. In conclusion, less than 3% of acromegalic patients developed CHF in this study. Although effective treatment of acromegaly improved short-term cardiovascular status, its impact on long-term survival is questionable.

Acromegaly↗