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Cytostatics for acromegaly. Marked improvement in a patient with an invasive pituitary tumour.

A 21-year-old woman suffering from acromegaly was treated with transsphenoidal subtotal hypophysectomy (microscopy: acidophilic adenoma), followed by x-ray and bromocriptine therapy. Seven years later she was re-operated because of a partial bitemporal loss of vision, intracranial hypertension, and regrowth of the pituitary tumour seen on CT-scan. A large part of the invasive suprasellar tumour was then removed by transcranial approach. The neurosurgery was followed by cobalt radiotherapy and bromocriptine administration. Two years later, symptoms and signs of tumour growth reappeared. Administration of cytostatics, such as doxorubicin (Adriamycin) and lomustine (Belustine), resulted in distinct clinical improvement associated with a seven-fold decrease in the serum growth hormone concentration. The visual field became normal and the intracranial mass on a CT scan decreased markedly. As a result the patient was able to resume work.

Acromegaly↗

Small airway function in acromegaly.

Small airway function was studied in 21 acromegalic patients (13 females, 8 males) and quantitated as the maximal expiratory flow at 25 and 50% of vital capacity (VEmax25, VEmax50) breathing room air, as the difference of flow at 50% of VC breathing air and 80% helium 20% O2 (delta Vmax50) and as the volume of equal flows (VisoV). In addition, lung volumes were investigated by spirometry and body plethysmography. Static lung volumes were statistically significantly increased in both male and female acromegalic patients (p less than 0.05), but RV/TLC and FEV1/FVC did not change (p greater than 0.1). VEmax25, delta Vmax50 and VisoV showed an abnormal function of small airways in nonsmoking acromegalic patients. However, smoking acromegalics did not differ significantly from 'normal' smoking subjects, suggesting that the dysfunction of small airways is not a contributory factor to mortality from the disease. Maximal expiratory flows, when related to lung volume, were reduced in acromegalic women. Abnormal small airway function in acromegaly could either be due to obstruction or, more likely, to an exaggeration of dysanaptic lung growth.

Acromegaly↗

Bromocriptine reduces growth hormone in acromegaly.

We assessed serum growth hormone (GH) levels in ten patients with acromegaly during a 24-hour profile and a 75-g oral glucose tolerance test (GTT). Serum GH levels were measured after five weeks of bromocriptine mesylate therapy, 20 mg daily (P1), after five weeks without bromocriptine mesylate therapy (P2), and again five weeks following restarting treatment with bromocriptine, 20 mg daily (P3). During the 24-hour profile, the following occurred: (1) mean serum GH level of the group was lower during P1 (20.5 mU/L) and P3 (20.8 mU/L) than P2 (49.6 mU/L); (2) in six individual patients during P1 and P3, there was a significant reduction in the mean serum GH value; and (3) a marked circadian variation in the serum GH value was present both with and without the drug therapy in five patients. During the GTT, the mean serum GH value was lower during P1 (18.4 mU/L) and P3 (16.7 mU/L) than P2 (43.3 mU/L), and in seven individual patients during P1 and P3, there was a significant reduction in the mean serum GH value. Overall, a clear reduction in serum GH values due to bromocriptine was demonstrated. In individual patients, serum GH values during a 24-hour profile and GTT gave similar indications of response.

Acromegaly↗

Acromegaly. The effects of various steroid hormones on the insulin-induced growth hormone response.

The availability of a sensitive assay for human growth hormone has made it possible to directly measure the effects of various agents purported to alter growth patterns. Acromegalic patients present a special problem both in early diagnosis and in therapy. Being able to measure growth hormone in these patients provides an accurate index of activity and a precise measure of therapeutic effectiveness. In an attempt to determine whether a pituitary block of growth hormone secretion is feasible in this condition, a study was made of the effects of estrogen, androgen and glucocorticoid administration on growth hormone response to a standard insulin tolerance test in a patient with active acromegaly. In the dosage schedules used in this study, it was not possible to suppress either basal growth hormone secretion or blunt its responsiveness to the normal physiologic stimulus of hypoglycemia.

Acromegaly↗

Response of plasma insulin to small doses of tolbutamide in obesity and acromegaly.

The early response of plasma insulin (IRI) to successive intravenous doses of 50, 100 and 200 mg of tolbutamide was studied in nondiabetic obese subjects, in acromegalic patients, and in healthy controls. The smallest dose raised the plasma IRI level within two minutes in all subjects. The insulin response was correlated with the basal IRI in controls and in obese subjects but not in acromegalic patients. At each tolbutamide dose level the mean IRI response of obese subjects was about three times greater than in controls. In acromegalic subjects an increased response was observed only after the 200 mg dose of tolbutamide. The results suggest that in obesity the stimulus-secretion coupling of insulin output is normal but the number of secretory units is increased. In acromegaly the insulin release pattern is compatible with an increased number of secretory units which, however, are relatively insensitive to tolbutamide, probably due to an elevated serum growth hormone level.

Acromegaly↗

[The heart in acromegaly: an echocardiographic study].

Clinical examinations including echocardiography were performed for 14 acromegalic patients (five men and nine women, whose mean age was 48.6 years). Three of these had hypertension (HT) above 160/95 mmHg, three had diabetes mellitus (DM). Their cardiac sizes and functions were correlated with the durations of disease and plasma growth hormone (GH) levels. The incidences of HT and DM were also evaluated. Three of 14 patients (22%) had increased cardiothoracic ratios (greater than 55%). Electrocardiographic abnormalities were noted in three patients including two with left ventricular hypertrophy (LVH) and one with interventricular conduction defects with abnormal Q waves. By echocardiography (Table 2), nine patients (64%) were judged to be normal. The remaining five patients (36%) had abnormal echocardiograms. These included LVH (sums of the interventricular and posterior wall thicknesses greater than or equal to 25 mm) in two (25 mm in Case 10, 30 mm in Case 11), increased left ventricular end-diastolic dimension (EDD greater than or equal to 55 mm) in one (72 mm in Case 14) and both abnormalities in two patients (Cases 12 and 13). Two patients (Case 13 and 14), whose %FS were 17% and 22%, respectively, had definite evidence of congestive heart failure. Two patients (Case 11 and 13) met the diagnostic criteria for asymmetric septal hypertrophy. One patient with echocardiographic LVH and another who had increased EDD with LVH had histories of HT (Case 11 and 12). Plasma GH levels in patients with LVH were greater than 100 ng/ml (Cases 10 and 11). The left ventricular hypertrophy and/or increased EDD observed in these patients seemed related to the duration of acromegaly but not to the presence of DM. Myocardial biopsy of the right ventricle in two patients with congestive heart failure disclosed myocardial hypertrophy, myocardial fiber disarray, interstitial fibrosis and large nuclei.

Acromegaly↗

Variation in plasma and urinary inorganic phosphate and pyrophosphate in normal subjects and in patients with acromegaly or osteoarthritis.

Plasma inorganic pyrophosphate (PPi) and inorganic orthophosphate (Pi) levels, urinary PPi and Pi excretion were measured every 2 h for a day in 4 normal subjects on a normal diet and again while fasting; 5 patients with osteoarthritis and 4 patients with acromegaly were also studied. Plasma Pi values were elevated at night in all subjects and were highest in the acromegalic patients. Mean plasma PPi was lower during fasting and correlated with Pi levels in all non-fasting subjects. Urinary Pi and PPi were strongly correlated; both were lower in fasting subjects. Food intake and the time of blood sampling are important biological variables that must be considered when interpreting plasma PPi levels.

Acromegaly↗

[Cauda equina syndrome and ankylosing spondylitis. Association with acromegaly. A myelographic and tomodensitometric study of the lumbar canal].

Cauda equina syndrome is a rare neurological complication of ankylosing spondylitis. The specific myelographic and tomodensitometric anomalies are exemplified by the reported observation. This case is unusual by the moderation of the neurological manifestations, and especially by the absence of sphincteral disorders. The characteristic roentgenologic signs of ankylosing spondylitis are associated with a scalloped appearance of the lumbar spinal column and antecedent quiescent acromegaly.

Acromegaly↗

[Insulin, glucagon and C-peptide content in the blood of acromegaly patients].

The content of pancreatic hormones and their relationship with the degree of carbohydrate metabolism disorder as well as the somatotropin level were studied in 26 patients with acromegaly. It was found that the degree of carbohydrate metabolism disorder is not dependent on the increase extent in the growth hormone concentration. Hyperinsulinemia was practically revealed in all the patients regardless of the glycemic curve type. There was no correlation between glycemia and insulin indices as well. It was determined that hyperglucagonemia provokes no carbohydrate metabolism injury.

Acromegaly↗

[Acromegaly and its orthopedic manifestations].

A review of the orthopaedic manifestations of acromegaly has been carried out from a study of literature. A further special study of 83 acromegalic patients reveals that about one third consulted the specialist for surgical intervention. In 14 of 28 patients a surgical intervention became necessary. The most frequent cases in question were nerve decompression. Recovery and success rate were always satisfactory.

Acromegaly↗

Growth activities of the nasal septal cartilage in acromegaly.

Growth activity in different areas of human septal cartilage was measured by in vitro incorporation of 35 S-labelled sulfate and 3 H-labelled thymidine in 6 acromegalic patients. Septal cartilage was obtained during transnasal hypophysectomy. The growth activities in the posterior area, which is situated anterior to the septo-ethmoidal junction were significantly enhanced compared to a control group of hormonally normal adults. Growth activities of the septal cartilage in the anterior free end and the suprapremaxillary area were not different in both groups. This indicates that growth hormone excess in acromegaly enhances human septal growth by stimulation of growth activities in the posterior area and not at the anterior free end and suprapremaxillary area.

Acromegaly↗

[Carcinoma of the hypophysis with acromegaly].

A 38-year old man deceased after being operated on recurring pituitary adenoma removed 13 years ago. Autopsy showed a massive spread of tumour on dura and in subarachnoid space. Growth hormone producing cells were found prevailing in the primary tumour as well as in secondaries by immunohistochemistry and immunofluorescence which concurred with acromegaly. Many cells produced prolactin. The tumour spreading discontinually in subdural and subarachnoid space was taken for a carcinoma.

Acromegaly↗

[Long-term use of parlodel in acromegaly].

The authors studied the basal and L-DOPA-stimulated levels of STH and basal level of prolactin in blood serum of 128 patients presenting with acromegaly. The basal levels of STH and prolactin were found to be elevated in the majority of patients with an active disease stage. Long-term (for 5-6 years) therapy with parlodel (2.5-20 mg a day) produced a disease remission. It is concluded that parlodel can be used not only as an additional agent to x-ray therapy or hypophysectomy but also as monotherapy, provided that the drug is applied for a long time.

Acromegaly↗

[Strategy for hormonal study in the arterial hypertension of acromegaly].

High blood pressure occurs in about 25 p. 100 of acromegalic patients. The mechanisms involved are unknown but an unusual incidence of Conn's syndrome has been reported in acromegaly. The development of hypertension may be favored by the chronic hydro-saline inflation dependent upon the growth hormone excess. Sodium inflation is likely to be responsible for abnormal responses to angiotensin II and its antagonists in normotensive acromegalics, which make the use of these agents inappropriate for the study of the renin-angiotensin-aldosterone system. The latter can be profitably explored by the measurement of hormonal blood levels which increase normally in response to Na deprivation and orthostatism. In cases of associated Conn syndrome, the urinary level of tetrahydro-aldosterone may be normal, aldosterone being metabolized through other pathways. This appears to be independent to growth hormone hypersecretion.

Acromegaly↗

[Dynamic evaluation of prolactin secretion in acromegaly (author's transl)].

The basal PRL levels and after estimulation with synthetic TRH were evaluated in 12 patients with active acromegaly, and in 12 normal individuals. None of the patients had galactorrhea and 5 of them had tumoral supra-sellar extension. Basal hyperprolactinemia was detected in 66% of the patients. After TRH stimulation, only 4 patients exhibited a percentual increment greater than 100% over the PRL basal value. PRL response to TRH was negative in 8 patients. The high PRL levels can be explained by the parallel production of GH and PRL by the tumoral cells, nevertheless a disturbance of the normal hypothalamic control cannot be excluded.

Acromegaly↗

Oral thyrotropin-releasing hormone (TRH) test in acromegaly.

UNLABELLED: The effects of 40 mg oral and 200 microgram intravenous TRH were studied in patients with active acromegaly. Administration of oral TRH to each of 14 acromegalics resulted in more pronounced TSH response in all patients and more pronounced response of triiodothyronine in most of them (delta max TSh after oral TRh 36.4 +/- 10.0 (SEM) mU/l vs. delta max TSH after i.v. TRH 7.7 +/- 1.5 mU/l, P less than 0.05; delta max T3 after oral TRH 0.88 +/- 0.24 nmol/vs. delta max T3 after i.v. TRH 0.23 +/- 0.06 nmol/l, P less than 0.05). Oral TRH elicited unimpaired TSH response even in those acromegalics where the TSH response to i.v. TRH was absent or blunted. In contrast to TSH stimulation, oral TRH did not elicit positive paradoxical growth hormone response in any of 8 patients with absent stimulation after i.v. TRH. In 7 growth hormone responders to TRH stimulation the oral TRH-induced growth hormone response was insignificantly lower than that after i.v. TRH (delta max GH after oral TRH 65.4 +/- 28.1 microgram/l vs. delta max GH after i.v. TRH 87.7 +/- 25.6 microgram/l, P greater than 0.05). In 7 acromegalics 200 microgram i.v. TRH represented a stronger stimulus for prolactin release than 40 mg oral TRH (delta max PRL after i.v. TRH 19.6 +/- 3.22 microgram/, delta max PRL after oral TRH 11.1 +/- 2.02 microgram/, P less than 0.05). CONCLUSION: In acromegalics 40 mg oral TRH stimulation is useful in the evaluation of the function of pituitary thyrotrophs because it shows more pronounced effect than 200 microgram TRH intravenously. No advantage of oral TRH stimulation was seen in the assessment of prolactin stimulation and paradoxical growth hormone responses.

Acromegaly↗

The clinical presentation and biochemical diagnosis of acromegaly and gigantism.

Over a 5-year period 14 patients with acromegaly and gigantism were seen at the endocrine clinic of King Edward VIII Hospital: 9 were Blacks and 5 Indians; 8 of the patients were women. The mean age of the patients was 46 years. Surprisingly, only 2 patients complained of acral overgrowth. Symptomatology was varied and not characteristic of the condition. On examination all patients had unequivocal signs of soft-tissue and bony overgrowth, 64% had visual abnormalities and 50% hypertension. Radiologically, 88% showed an enlarged pituitary fossa. On biochemical investigation, the fasting levels of growth hormone (GH) were increased in 12 patients and during oral glucose tolerance tests, the GH levels in these 12 patients were not suppressed. One patient in whom the fasting GH level was not increased had progressed to the stage of panhypopituitarism, in the remaining patient challenge with thyrotrophin-releasing hormone (TRH) led to increased GH levels and L-dopa challenge resulted in a paradoxical decrease in GH levels. Seven patients with increased GH levels who were challenged with L-dopa showed the typical decrease in GH levels found in this condition; in 5 of these patients, challenged with TRH, GH levels increased. The findings emphasize that despite the ease of clinical diagnosis, appropriate biochemical investigations are necessary to confirm the exact status of the disease, which is rare in the population studied.

Acromegaly↗