Diagnosis and treatment of acromegaly

Acromegaly is an insidious disease that occurs, in the majority of cases, as a result of a pituitary adenoma that hypersecretes growth hormone (GH). The clinical consequences of acromegaly are a function of excess GH secretion and mass effect of the pituitary tumor. The involvement of multiple organ systems may lead to significant morbidity and mortality, prompting the need for rapid and accurate disease recognition and treatment. This brief review will describe current recommendations for management of this uncommon, but debilitating, endocrine disorder.     

Efficacy and complications of neurosurgical treatment of acromegaly

The aim of the study was to evaluate the frequency of occurrence of pituitary failure following neurosurgery and the efficacy of transsphenoidal tumour resection in acromegalic patients. We retrospectively evaluated 85 patients (60 female and 25 male), of mean age 43.9 ± 13.2 years, treated by transsphenoidal neurosurgery. Macroadenoma and microadenoma of pituitary were found in 66 (77.6%) and 19 (22.4%) of these patients, respectively. Criteria of cure following neurosurgery were: basal GH < 2.5 μg/l, GH at 120 min in OGTT < 1.0 μg/l and serum concentration of IGF-1 within normal ranges for age and sex. After surgery 32 patients (37.6%) were cured and 53 patients (62.4%) required somatostatin analogue treatment. In patients cured by surgery, lower levels of basal GH (P < 0.05), IGF-1 (P < 0.001), GH at 120 min in OGTT and smaller size of pituitary tumour (P < 0.05) were found at diagnosis, as compared to patients in whom surgery was unsuccessful. Significant correlation between basal serum level of GH at diagnosis and size of pituitary tumour was found (P < 0.001). Invasive tumours were found in 45 of 53 (84.9%) patients not cured and in only 8 of 32 (25.0%) patients cured (P < 0.001). Impaired function of pituitary anterior lobe after surgery was observed in 30% and 4% of patients with macro- and microadenoma, respectively (P < 0.05). The efficacy of neurosurgery is affected by concentration of basal serum GH and IGF-1, GH at 120 min in OGTT, tumour size and invasiveness. Hypopituitarism after surgery is more frequent in patients with macroadenoma. Pituitary insufficiency, as a consequence of surgery, was found in 21% of patients with normal pituitary function prior to operation.     

A consensus on the diagnosis and treatment of acromegaly complications

In March 2011, the Acromegaly Consensus Group met to revise and update the guidelines on the diagnosis and treatment of acromegaly complications. The meeting was sponsored by the Pituitary Society and the European Neuroendocrinology Association and included experts skilled in the management of acromegaly. Complications considered included cardiovascular, endocrine and metabolic, sleep apnea, bone diseases, and mortality. Outcomes in selected, related clinical conditions were also considered, and included pregnancy, familial acromegaly and invasive macroadenomas. The need for a new disease staging model was considered, and design of such a tool was proposed.     

Cardiovascular complications in acromegaly

Cardiovascular morbidity and mortality are increased in acromegaly. In fact, GH and IGF-I excess induces a specific cardiomyopathy. The early stage of acromegaly is characterized by the hyperkinetic syndrome (high heart rate and increased systolic output). Frequently, concentric biventricular hypertrophy and diastolic dysfunction occur in acromegaly, leading to an impaired systolic function ending in heart failure if the disease is untreated or unsuccessfully untreated. Besides, abnormalities of cardiac rhythm and of valves have been also described in acromegaly. The coexistence of other complications, such as arterial hypertension and diabetes, aggravates the acromegalic cardiomyopathy. The suppression of GH/IGF-I following an efficacious therapy could decrease left ventricular mass and improve cardiac function. In conclusion, a careful evaluation of cardiac function, morphology and activity seems to be mandatory in acromegaly.     

胰十二指肠切除术的主要并发症及诊断与治疗

0引言胰十二指肠切除术(PD)是腹部外科最复杂的手术之一,近年来,对胰腺和壶腹部肿瘤患者PD的应用逐渐增加,PD被认为一种安全、有效的手术.虽然PD在大的医疗中心术后死亡率已降至<5%[1],但1990年以来的资料显示胰十二指肠切除术后并发症仍高为25-35%[2-4].其术后除了一般腹部外科并发症以外,主要有胰漏、胆漏、出血、腹腔感染以及胃排空障碍等.如何防治这些致命的并发症,一直是腹部外科医生关注的热点.本文就近年来对上述并发症所采取的诊治措施进行探讨.1胰漏胰腺手术或胰腺周围脏器手术后腹腔引流液淀粉酶含量超过1000u/L,引流时间超过…     

肝硬化少见并发症的诊治

乳糜性及血性腹水、肝性胸水、少见病原菌感染的自发性腹膜炎、肝硬化心肌病、门静脉性肺动脉高压、肝硬化神经系统损伤等肝硬化少见并发症,临床医生尚缺乏充分的认识和/或及时有效的诊治。现介绍上述肝硬化少见并发症的临床特征、治疗及预后,以提高临床医生的认识和诊疗水平。     

Diagnosis and endocrine testing in acromegaly.

Acromegaly is a characteristic clinical syndrome resulting from excessive production of GH and SmC/IGF-I generally from a GH-producing pituitary tumor. Once the diagnosis is suspected on clinical grounds, it should be established based on persistent elevation of the basal GH, along with an increased SmC/IGF-I level; it is confirmed by a lack of suppressibility of GH levels following a glucose load. Other tests, including the paradoxic GH elevation in response to TRH and LHRH, are helpful in establishing the diagnosis, as well as determining and monitoring the outcome of surgical and medical therapy. The past few years have been enriched with new knowledge in the area of IGF-binding proteins. Evidence of clinical correlation exists regarding GH status, IGF-I levels, and the IGFBPs particularly IGFBP-1 and IGFBP-3. The value of IGFBPs in clinical practice as a diagnostic tool in disorders of GH secretion appears promising, but further studies are required.     

Bromocriptine treatment of acromegaly

Bromocriptine at a dose of 7.5-30 mg/day was given to 12 acromegalics for 6 mo. Mean serum growth hormone (GH) levels during a glucose tolerance test (GTT) were significantly lowered by the drug. In four patients the serum GH response during a GTT was suppressed to normal (i.e. less than or equal to 5 mlU/liter). If bromocriptine had not brought the serum GH response to a GTT to normal at a dose of 20 mg/day, this effect was not achieved by raising the dose to 30 mg/day. Bromocriptine was effective for the duration of treatment. On discontinuing therapy there was an increase in serum GH levels. No obvious clinical changes in the acromegalic features were noted. One patient with impaired glucose tolerance and one with established diabetes had normal glucose tolerance while on bromocriptine and another two patients with impaired glucose tolerance showed no obvious changes while on the drug. Side effects were minor. X-rays of the pituitary fossa before starting and at the end of treatment showed no significant change. We conclude that although bromocriptine is the most promising form of medical treatment for acromegaly to date, it is fully effective only in a minority of patients.     

培维索孟治疗肢端肥大症

生长激素(Growth Hormone,GH)分泌过多,在骨骺尚未闭合时期不断促进长骨生长,使患者身高不断增长,称为巨人症;在骨骺已经闭合以后则促进扁骨等膜化骨增宽增厚,导致面容变形,手足增大,肢端变粗,称为肢端肥大症;如起病时骨骺尚未闭合而就诊时已闭合,则兼备二者的临床表现,称为肢端肥大性巨人症.     

Estrogen treatment for acromegaly

Estrogens have been used in patients with acromegaly since the 1930?C1940s, suppressing plasma IGF-1 levels and improving clinical signs and symptoms of acromegaly. Estrogens antagonize GH function at the post-receptor level, inhibiting GH signaling, thus decreasing GH-induced hepatic IGF-1 synthesis. We report our experience with four female patients with active acromegaly, na?ve to medical treatment or inadequately controlled by somatostatin receptor ligands (SRLs) or the GH-receptor antagonist. Adding estrogen treatment (contraceptive pills or transdermal estrogen patches) to their ongoing medical treatment, suppressed IGF-1 significantly in all patients, achieving hormonal remission in three of them. We review the available data on the use of estrogens and selective estrogen receptor modulators in acromegaly, and their mechanisms of action. Estrogens could be an alternative, inexpensive adjuvant treatment for females with active acromegaly, who are only partially responding to SRLs or to the GH-receptor antagonist.     

Repeat endoscopic transsphenoidal surgery for acromegaly: remission and complications

Reported biochemical remission rates following surgical intervention for acromegaly range from 38 to 83 %. In patients not achieving surgical remission, few options remain, mostly limited to medical management and radiation therapy. There is debate over whether or not to offer reoperation to patients in whom surgical remission is not achieved with initial resection. Retrospective chart review was undertaken to determine all patients having acromegaly with persistently elevated GH and/or IGF-1 levels after initial pituitary adenoma resection, and who underwent reoperation using endoscopic endonasal approach at a single institution. Biochemical remission was defined as a postoperative GH level <1 ng/mL and a normal postoperative IGF-1 level in the absence of any medical therapy. In total, 14 patients underwent repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach. Of the 14 patients, 8 (57 %) achieved biochemical remission following repeat surgical intervention. Lower preoperative GH levels were associated with greater chance of biochemical remission (P = 0.048). New endocrinopathies were seen in 2 patients (14 %), and both were transient diabetes insipidus. Meningitis occurred in 2 patients (14 %); both were aseptic meningitis with no sequelae. No mortality was encountered. Repeat surgical intervention for acromegaly via endoscopic transsphenoidal approach appears safe and effective. With no mortality and minimal morbidity, repeat surgical intervention via endoscopic transsphenoidal approach appears a reasonable option for these hard-to-treat patients and should be considered for patients in whom surgical remission is not achieved with initial surgery.     

The surgical treatment of acromegaly

Purpose

Surgical extraction of as much tumour mass as possible is considered the first step of treatment in acromegaly in many centers. In this article the potential benefits, disadvantages and limitations of operative acromegaly treatment are reviewed.

Methods

Pertinent literature was selected to provide a review covering current indications, techniques and results of operations for acromegaly.

Results

The rapid reduction of tumour volume is an asset of surgery. To date, in almost all patients, minimally invasive, transsphenoidal microscopic or endoscopic approaches are employed. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. The radicality of adenoma resection essentially depends on localization, size and invasive character of the tumour. The normalization rates of growth hormone and IGF-1 secretion, respectively, depend on tumour-related factors such as size, extension, the presence or absence of invasion and the magnitude of IGF-1 and growth hormone oversecretion. However, also surgeon-related factors such as experience and patient load of the centers have been shown to strongly affect surgical results and the rate of complications. As compared to most medical treatments, surgery is relatively cheap since the costs occur only once and not repeatedly. There are several new technical gadgets which aid in the surgical procedure: navigation and variants of intraoperative imaging.

Conclusions

For the mentioned reasons, current algorithms of acromegaly management suggest an initial operation, unless the patients are unfit for surgery, refuse an operation or only an unsatisfactory resection is anticipated. A few suggestions are made when a re-operation could be considered.