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PubMed1999

Folliculo-stellate cells in pituitary adenomas of patients with acromegaly.

Pituitary adenoma tissue from patients with acromegaly (n = 286) was obtained by surgery and examined for folliculo-stellate cells by immunostaining for S100 protein. The number of immunostained cells varied from one adenoma to another. A hundred and ninety-eight pituitary adenomas (69%) contained S100 protein positive cells corresponding to folliculo-stellate cells (FSC): in 100 cases (35%), only few sparse FSC were found, in 43 cases (15%) FSC were scattered throughout the adenoma, and in 55 cases (19%) there was an abundance of FSC. There were no significant differences regarding sex or age of the patients. The relative amount of FSC vaired among different adenoma types. Plurihormonal adenomas showed the highest FSC density, whereas the majority of monohormonal adenomas contained only few or no FSC. Patients with pituitary adenomas containing scattered FSC had a significantly higher preoperative mean GH level than patients with pituitary adenomas not having FSC. There was a negative correlation between the FSC density in adenoma tissue and the preoperative mean PRL level. There was no correlation between the tumour size and the amount of FSC. Our data indicate no effect of the duration of symptoms on the FSC density and do not suggest a correlation between FSC density and the percentage of a certain hormone-secreting cell type.

Acromegaly↗
PubMed2006

Long-term primary medical therapy with somatostatin analogs in acromegaly.

To cure acromegalic patients, transsphenoidal surgery is considered first, especially for microadenoma. However, less than 50% of patients with macroadenoma achieve satisfactory biochemical control. Moreover, surgery may cause hypopituitarism. Medical therapy may offer the prospect of near normalization of growth hormone (GH)/insulin-like growth factor-1 levels with substantial tumor shrinkage in a significant number of patients. Here, we report two cases of acromegaly under treatment with somatostatin analogs alone for more than 10 years. Case 1 was a 54-year-old man with a pituitary macroadenoma. He received 4 years of octreotide treatment followed by 6 years of prolonged-release (PR) lanreotide resulting in normal GH level. Case 2 was a 60-year-old woman with a 1.3 cm pituitary tumor. She received 8 years of octreotide treatment followed by 6 years of PR lanreotide resulting in subnormal GH level and gallbladder sludge. She had received bilateral total hip replacement for hip osteoarthritis at the age of 59 years. These cases illustrate that long-term treatment with somatostatin analogs offers an alternative choice in selected acromegalic patients, such as those with pituitary tumor who cannot be cured by surgery, those who have unacceptable anesthetic risk and those who refuse surgery.

Acromegaly↗
PubMed1991

Typical changes in the viscerocranium in acromegaly.

31 patients (mean age 52.7 years) suffering from persistent symptoms of a growth hormone-producing pituitary adenoma underwent both clinical and radiological examination at least one year after transnasal extirpation of the tumour. The results of standardized X-ray analysis of the viscerocranium were compared with a group of 21 healthy subjects (mean age 42.1 years): Although several remarkable changes of the facial skeleton were observed, statistically significant changes could be found in the lower jaw only. The ascending ramus as well as the mandibular body were found to be elongated. The main contribution to the elongation was made by the chin prominence and the condyle. Two different growth patterns of the mandible could be determined; neither of them was pathognomonic for acromegaly. Due to overgrowth of the septal cartilage in 7 patients we found a so-called "hanging columella". In 16 patients the mandibular canal was widened and showed marked deviations in its diameter or a funnel-shaped mandibular foramen.

Acromegaly↗
PubMed2003

Long-term treatment outcome in acromegaly.

A number of groups have developed guidelines to indicate whether an individual with acromegaly has been cured by treatment. However, studies to date do not provide a robust definition of biochemical remission of the disorder based on correlation with long-term outcome. Available data suggest that those with a random serum growth hormone (GH) level of <2.5 microg/l, or a glucose-suppressed GH level of <1 microg/l following treatment have mortality figures indistinguishable from the general population. However, the confidence limits for these mortality estimates are quite wide. It remains possible that growth hormone levels lower than 1 microg/l for random samples, or even lower when using ultrasensitive GH assays, may indicate superior outcome, but this remains to be confirmed. There are limited data relating serum insulin-like growth factor-I (IGF-I) levels to outcome, although normalisation of serum IGF-I clearly improves outcome compared with continued elevation of measurements after treatment. Current evidence suggests that a post-treatment random serum GH <2.5 microg/l and a normal serum IGF-I value defines biochemical cure. Available data suggest that achieving similar growth hormone levels after treatment also reduces the prevalence of chronic complications of the disorder, which is subsequently reflected in improved mortality.

Acromegaly↗
PubMed2003

Metabolic effects of GH antagonism in patients with acromegaly.

Pegvisomant is a growth hormone (GH) receptor antagonist that represents a major advance in the treatment of acromegaly. Initial results with pegvisomant indicate this novel form of therapy to be the most effective treatment available for achieving biochemical disease control as ascertained by circulating IGF-I.

Acromegaly↗
PubMed1977

The treatment of acromegaly by Yttrium implantation.

Yttrium implantation is one of the many ways of treating acromegaly. The advantages are the minor nature of the procedure and the fact that pituitary replacement is not as commonly required as after hypophysectomy. Thus in young female patients menstruation may be resumed following treatment and pregnancy has occurred. The procedure is not as free from complications as external irradiation but the response is more satisfactory.

Acromegaly↗
PubMed1989

Growth hormone rebound after cessation of sms 201-995 treatment in acromegaly.

We studied a 42-year-old woman who had persistent active acromegaly despite conventional therapies. She was treated for 6 months with SMS 201-995. Her mean plasma growth hormone GH values decreased during treatment from 9.1 +/- 1.2 to 6.6 +/- 1.2 micrograms/L. One month after the withdrawal of SMS 201-995, the plasma GH level increased to 24.4 micrograms/L (P less than 0.001). This elevation was clinically silent and transitory, as GH levels decreased 8 months later to 6.9 +/- 1.3 micrograms/L. Furthermore, at the beginning of therapy, her intractable headache was completely relieved; however, it progressively resumed under therapy. In conclusion, cessation of SMS 201-995 may be followed in some acromegalic patients by a rebound of plasma GH levels. This rebound suggests that SMS 201-995 decreases GH levels by an inhibition of its release from the pituitary. Furthermore, SMS 201-995 may relieve intractable headache in some acromegalic patients, but tolerance to the analgesic effect may develop.

Acromegaly↗
PubMed1999

Retinitis pigmentosa in association with acromegaly: a case report.

Retinal abnormalities, unrelated to visual pathway compression, in acromegalic patients were originally described by Small in 1972 (Smail JM. Primary pigmentary degeneration of the retina and acromegaly in a case of pituitary adenoma. Br J Ophthalmol 1972; 56: 25-31). He illustrated a case of primary pigmentary degeneration of the retina occurring in a patient with a chromophobe adenoma of the pituitary gland. To the best of our knowledge this remains the sole, published case of this association. We report on two male patients, with an acromegalic appearance, one caused by a pituitary adenoma, the other associated with a Rathke's cleft cyst, presenting to our department of ophthalmology with the clinical picture of pigmentary degeneration of the retina.

Acromegaly↗
PubMed1999

Role of gamma knife radiosurgery in acromegaly.

Stereotactic radiosurgery with the Gamma Knife allows the delivery of focused radiation in a single session from a Cobalt-60 source to a pituitary tumor with little radiation to surrounding normal brain tissue. At this time the major role for Gamma Knife radiosurgery in acromegaly is for the treatment of failed pituitary surgery although it may also by used as primary treatment for patients unwilling or unsuitable, for medical reasons, to undergo transsphenoidal surgery. The major risk from Gamma Knife radiosurgery appears to be radiation damage to the visual pathways, but this can be obviated by limiting the radiation dose to the optic chiasm under 10 Gy. In contrast, the neuronal and vascular structures running in the cavernous sinus are much less radiosensitive allowing an ablative dose to be administered to tumors showing lateral invasion and impinging on cranial nerves III, IV, V and VI. Gamma Knife radiosurgery appears to produce effects in GH secreting tumors faster than with fractionated radiotherapy without the potential long-term risk of developing a second extrapituitary brain tumor as well as the neuropsychiatric effects associated with conventional radiation administration.

Acromegaly↗
PubMed1999

New medical treatment for acromegaly.

The available somatostatin analogs for subcutaneous administration lower growth hormone (GH) levels in more than 90% of patients and Insulin-like growth factor-I (IGF-I) levels in up to 60%. They are also capable of reducing tumor size in up to 50%. Recently long-acting somatostatin analogs were introduced. The use of these application forms can result in normalization of IGF-1 in 60% of patients after 1 year and in 75% after 3 years. The development of selective analogs for the somatostatin receptor subtype-5 potentially will enhance the potency and the spectrum of the medical treatment of acromegaly with somatostatin analogs. The new generation of dopaminergic drugs also form a potentially effective and well tolerated therapy that should be considered in the management of those acromegalic patients, which have relative low serum IGF-I concentrations, along with high serum prolactine levels. Finally, growth hormone receptor (GHR) antagonists are under development for the use in humans. Preliminary results look promising, when biochemical parameters are concerned. Interim analysis of a phase 3 study with B2036-PEG in 38 patients does show that normalization of IGF-I concentrations is reached in at least 92% of the treated patients.

Acromegaly↗
PubMed1999

Cardiovascular effects of a single slow release lanreotide injection in patients with acromegaly and left ventricular hypertrophy.

In our study we assessed the effects of a single i.m. injection of slow-release Lanreotide (30 mg) (SR-L), a new long-acting somatostain analog, on circulating GH levels, baseline cardiac function (M-mode, 2D guided, doppler-echocardiographic study) and cardiopulmonary response to exercise (cycloergometric test, performed using a computer drived, electrically braked cycle ergometer), tested at baseline, after 7 and 14 days from the injection in 10 acromegalic patients (5 M, 5 F, mean age 57.7 +/- 3.1 yrs, body mass index (BMI) 27 +/- 0.8 kg/m2, blood pressure 141 +/- 6.5/82 +/- 3 mmHg). SR-L administration decreased GH levels in acromegalic patients (mean +/- SEM) from 16.1 +/- 6.9 to 10.8 +/- 5.1 micrograms/L (p = 0.045) after 7 days and to 11.9 +/- 5 micrograms/L (p = 0.078) after 14 days from the injection. Moreover, we observed a significant (p < 0.05) decrease in systolic blood pressure and heart rate at the 7th (135 +/- 6.1 vs 141 +/- 6.5 mmHg, and 68 +/- 2.1 vs 74 +/- 2.1 bpm) and 14th (137 +/- 6.2 vs 141 +/- 6.5 mmHg, and 72 +/- 2 vs 74 +/- 2.1 bpm) day of the study with respect to the baseline values. After SR-L administration we also found an increase in ejection fraction (69 +/- 2 vs 63 +/- 2.3% at 7th day, p = 0.006; 65 +/- 2.3 vs 63 +/- 2.3% at the 14th day, p = 0.027) and shortening fraction (40.8 +/- 1.8 vs 36.6 +/- 1.9% at 7th day, p = 0.005; 38.7 +/- 1.8 vs 36.6 +/- 1.9% at the 14th day, p = 0.045). The positive acute cardiac response to SR-L injection was also demonstrated by the increase in A/E velocity ratios at 7th (1.14 +/- 0.1 vs 0.98 +/- 0.07, p = 0.016) and 14th (1.04 +/- 0.08 vs 0.98 +/- 0.07, p = 0.008) day of the study. After SR-L injection, exercise capacity and VO2 at anaerobic threshold were also increased with respect to the baseline test: 61.1 +/- 8.2 vs 38.9 +/- 6.8 watts (p = 0.002) and 1012.4 +/- 71.5 vs 915.3 +/- 77.8 mL/min (p = 0.033) after 7 days, and 61.4 +/- 7.2 vs 38.9 +/- 6.8 watts (p = 0.002) and 1010.1 +/- 62.5 vs 915.3 +/- 77.8 mL/min (p = 0.010) after 14 days from the injection. In conclusion, these results suggest that in acromegalic patients: (1) SR-L causes a rapid improvement in baseline cardiac function and in cardiopulmonary performance during exercise in acromegaly; (2) the endocrine (decrease in GH levels) and echocardiographic responses to SR-L are maximal after 7 days from the injection, whereas the effect of SR-L on the exercise performance are longer lasting.

Acromegaly↗
PubMed2000

Time course of GH and IGF-1 levels following withdrawal of long-acting octreotide in acromegaly.

AIM: Several studies have demonstrated the efficacy of octreotide LAR administered intramuscularly at 4-week intervals in the treatment of acromegaly. In contrast, few data are available on the time course of GH and IGF-1 plasma levels following octreotide LAR withdrawal. This prompted us to study these parameters for up to 20 weeks following drug withdrawal in a group of 18 acromegalic patients treated for one year. DESIGN AND PATIENTS: We studied 18 patients treated with octreotide LAR 10 mg (n = 2), 20 mg (n = 15) and 30 mg (n = 1) every 4 weeks for one year. GH (mean level during a 4-hour daily profile) and IGF-1 concentrations were measured at the end of treatment, just before the last injection (baseline) and then 15 +/- 2 weeks (first control) after the last injection. In patients with GH levels below 2.5 micrograms/L and/or normal IGF-1 at the first control, a second control was performed four to eight weeks later. RESULTS: After one year of treatment with octreotide LAR, the mean plasma GH concentration was 1.91 +/- 1.25 micrograms/L (mean +/- SE) and the mean IGF-1 concentration was 440 +/- 251 micrograms/L. Among the 18 patients, 13 had mean plasma GH concentrations below 2.5 micrograms/L and seven could be considered as well-controlled (normal IGF1 and mean GH levels below 2.5 micrograms/L). After treatment withdrawal, the plasma GH concentration remained below 2.5 micrograms/L at the first and the second controls in 2 of the 13 (15%) patients with suppressed GH levels on baseline. Among the seven well-controlled patients on baseline (GH levels below 2.5 micrograms/L and normal IGF-1), one (15%) remained well-controlled, one (15%) kept GH levels below 2.5 micrograms/L but increased IGF-1 levels, and one (15%) kept normal IGF-1 levels but increased mean GH levels at the first control. This hormonal status remained unchanged at the second control in these 3 patients. CONCLUSIONS: These results show long-lasting suppression of GH secretion after treatment withdrawal in some acromegalic patients treated for 12 months with octreotide LAR. The duration of GH suppression after treatment withdrawal is variable. Mean GH levels remained below 2.5 micrograms/L in 15% of our patients for up to 21 weeks following withdrawal of octreotide LAR. In practice, it may be preferable to wait several months after long-acting somatostatin analog withdrawal before reassessing hormone status. Owing this long-lasting effect, a dose reduction to 10 mg and/or a longer interval between injections could be considered for very good responders, as this would lead to considerable cost savings without affecting GH or IGF-1 control.

Acromegaly↗
PubMed2000

Hepatolithiasis (intrahepatic stone) during octreotide therapy for acromegaly: a case report.

We report a case of hepatolithiasis (intrahepatic stone) complicated by gram-negative sepsis in a 37 year old male with acromegaly being treated with octreotide. As a child, he had suffered a traumatic injury to his liver requiring the surgical repair of a laceration. This is the first reported case of hepatolithiasis during octreotide therapy. Gallstones and bile sludge are common side effects of octreotide therapy but rarely become symptomatic or require treatment. Hepatolithiasis is uncommon in western countries but is quite prevalent in East Asia and is often associated with a predisposing condition that causes intrahepatic bile stasis (eg. bile duct stricture). In addition to its known effect on gallbladder stasis, octreotide alters bile acid composition and may thus hasten intrahepatic sludge and stone formation. Extra caution should be taken in using octreotide or its long-acting analog in patients otherwise predisposed to intrahepatic bile stasis.

Abdominal Pain↗
PubMed2001

Acromegaly: historical perspectives and current therapy.

Soon after the initial description of acromegaly in the late 19th century, neurosurgeons performed the first operative procedures for the disease. Transcranial procedures eventually yielded to the transsphenoidal approach. Reasonably effective medical therapy was introduced in the 1970s and pharmacological progress continues to be realized. It is now recognized that excess growth hormone is associated with significant morbidity and mortality and that biochemical remission improves outcome. Although medical and radiation treatments offer useful adjuncts, surgery provides optimal results.

Acromegaly↗
PubMed2006

Acromegaly with moderate hyperprolactinemia caused by an intrasellar macroadenoma.

BACKGROUND: A 31-year-old woman presented 12 months after discontinuing the oral contraceptive pill with progressive headache to her primary-care physician. She had previously presented with irregular menses to her obstetrician-gynecologist 4 months after discontinuing the oral contraceptive pill. Her serum prolactin levels were 153 microg/l and a pituitary MRI revealed a 13 mm intrasellar mass consistent with an adenoma. The patient was given 0.5 mg cabergoline twice weekly, and after 6 weeks her prolactin levels fell to 31 microg/l. After 6 months, however, she complained of persistent frontal headache and a repeat MRI revealed that the adenoma had increased in size to 16 mm. The patient was referred to an endocrinologist for further evaluation. INVESTIGATIONS: Serum insulin-like growth factor 1 levels and growth hormone levels measured 2 h after ingestion of 75 g of oral glucose. DIAGNOSIS: Acromegaly and hyperprolactinemia caused by a mixed-cell adenoma, secreting growth hormone and prolactin. MANAGEMENT: Trans-sphenoidal surgery followed by medical therapy with 20 mg intramuscular octreotide-LAR monthly.

Acromegaly↗
PubMed2001

Altered circadian blood pressure profile in patients with active acromegaly. Relationship with left ventricular mass and hormonal values.

To determine the relationships between the circadian blood pressure profile and left ventricular mass, hormonal pattern and insulin sensitivity indices in patients with active acromegaly, ambulatory 24-h blood pressure monitoring (ABPM) was recorded in 25 subjects (47.0 +/- 15.1 years, range 23-72). Serum growth hormone (GH) and insulin-like growth factor-1, fasting and mean plasma glucose and insulin during oral glucose tolerance test (OGTT), insulinogenic index, the sum of the plasma insulin levels and the homeostasis model insulin resistance index (Homa's index) were determined. Left ventricular mass index (LVMI) was calculated from two-dimensional guided M-mode echocardiogram. The prevalence of hypertension was 56% (n = 14) and 40% (n = 10) according to sphygmomanometric measurements and ABPM, respectively. Non-dipping profile was observed in six of 10 hypertensives and in six of 15 normotensives. Serum growth hormone, fasting glucose, the area under the serum insulin curve and LVMI were higher for acromegalics with non-dipping profile than for dippers (all of them, P < 0.05). In non-dippers daytime heart rate was higher than night time (P < 0.001). In conclusion, the main observations in the present study suggested that both normotensive and hypertensive acromegalics had a highly prevalent non-dipping profile with a preserved circadian pattern of heart rate, that was associated with higher levels of serum GH. The disturbance in nocturnal blood fall in normotensives was associated with a decreased insulin sensitivity. The role of GH in blood pressure circadian rhythm regulation in essential hypertension deserves further studies.

Acromegaly↗
PubMed2004

Surgical orthodontic correction of acromegaly with mandibular prognathism.

A male (30 years five months) who complained of mandibular prominence and masticatory dysfunction was diagnosed as a mandibular prognathic with acromegaly after cephalometric and endocrine examinations. The level of growth hormone (GH) subsequent to a transsphenoidal hypophysectomy had been controlled by medicines for about five years. Surgical orthodontic correction improved his occlusion and profile, but magnetic resonance imaging detected a recurrent adenoma in the cranial base during the retention period. The recurrence resulted in slight prognathic changes of the patient with a high level of GH. This is a case report of the treatment of an acromegalic patient discussing growth considerations that could influence the orthodontic treatment plan and long-term stability.

Acromegaly↗
PubMed1999

Acromegaly and papillomatosis: difficult intubation and use of the airway exchange catheter.

We describe the anaesthetic management of a patient with acromegaly scheduled for transsphenoidal resection of a pituitary tumour who was found at intubation to have coexisting laryngeal papillomatosis. Oral intubation was impossible using both direct and fibreoptic techniques. Nasal fibreoptic intubation was successful but precluded the transsphenoidal approach to surgery. A Cook Airway Exchange Catheter [Cook (UK) Ltd, Monroe House, Letchworth SG6 1LN] was used with a Negus bronchoscope to convert to oral intubation and allow completion of surgery without resort to tracheostomy.

Acromegaly↗