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[TRH-stimulated growth hormone secretion in acromegaly. Therapeutic results with 188 patients].

TRH-induced stimulation of hGH secretion before and after operation or radiotherapy and during bromocriptine treatment was tested in 188 patients with acromegaly. A normal hGH level (basal level less than 5 ng/ml) was achieved after operation in 106 patients (58%). Postoperatively persisting elevated hGH levels were reduced to normal by bromocriptine in 39%, by radiation in 22% and by combined radiation and bromocriptine in 48%. In cases with additional hyperprolactinaemia a response to bromocriptine occurred in 47%. Pre- and postoperative TRH-induced stimulation of hGH secretion was not correlated with the rate of either normalization nor recurrence and thus has no prognostic significance.

Acromegaly↗

Evaluation of acromegaly by radioimmunoassay of somatomedin-C.

We measured serum concentrations of somatomedin-C by radioimmunoassay in 57 acromegalic patients and compared them with various indicators of disease activity. The mean fasting somatomedin-C concentration was 6.8 U per milliliter (range, 2.6 to 21.7) for the acromegalics and 0.67 U per milliliter (range, 0.31 to 1.4) for 48 normal, fasting adults. The somatomedin-C concentration correlated significantly with: heel-pad thickness (r = 0.73), fasting glucose (r = 0.74), and one-hour postprandial glucose (r = 0.77). In contrast, "glucose-suppressed" growth hormone correlated weakly (r = 0.34, 0.36, 0.34) with these clinical indexes of severity. Fasting growth hormone levels showed no correlation (r = 0.14). Five active acromegalics had "normal" growth hormone levels after glucose suppression, but they had elevated somatomedin-C. In 15 patients studied one year after treatment, changes in somatomedin-C concentrations paralleled the degree of clinical improvement. Measurement of somatomedin-C appears to provide a reliable means for confirming the diagnosis of acromegaly and of clinical disease activity than measurement of growth hormone concentrations.

Acromegaly↗

Elevated levels of smooth muscle autoantibodies in patients with acromegaly.

Screening of sera from patients with central nervous system (CNS) tumors for serum antibodies to tumor and normal tissue antigens revealed that the sera from a significant percentage of patients with pituitary adenoma demonstrated reactivity for smooth muscle antibodies (SMA) at a serum titer (1/25) at which other CNS tumors are devoid of this reaction. The sera were assessed by an indirect immunofluorescent antibody assay on fresh cryostat sections of rat kidney, liver, diaphragm, and stomach tissue. Absorption of SMA-positive sera with extracts containing smooth muscle tissue abolished the reaction. The overall incidence of SMA among patients harboring pituitary tumors was 30% (12/40). Assessment of the functional types of the tumor revealed a distinct predilection for such findings among patients with clinical acromegaly. Among patients with hypersecretion of growth hormone (CA) 90% (9/10) have SMA (both IgG and IgM type) whereas SMA was positive in only 10% (3/30) of corresponding group of patients with pituitary tumors resulting in hypercortisolemia or those that did not result in a hyperfunctional endocrine state.

Acromegaly↗

Acromegaly in the developing world--a 20-year teaching hospital experience.

A retrospective analysis was conducted to examine the long-term outcome of surgery, by a single pituitary surgeon and radiotherapy for acromegaly at Groote Schuur Hospital, Cape Town, using modern criteria for the definition of cure. Seventy-two patients (F/M ratio 1.3:1), aged 16-74 years, were eligible for inclusion. The mean follow-up period was 8.3 years. Macroadenomas were present in 79%, microadenomas in 15% and tumour size was not documented in 6%. Pretreatment GH levels were, > or = 40 m U/l in 56 patients. Postoperatively, 21% of patients were cured, 40% controlled and 40% had hypopituitarism. After radiotherapy (mean follow-up 8.7 years) 43% were cured, 66% controlled and 78% had hypopituitarism. At follow-up 37% of patients traced had died. The most common cause of death was vascular disease. The poor surgical results may be attributed to late presentation in the developing world setting, as evidenced by tumour size and invasiveness, and the degree of GH elevation. Emphasis on early diagnosis of non-invasive tumours is necessary to improve the cure rate and reduce mortality,

Acromegaly↗

Acromegaly due to an ectopic pituitary adenoma in the sphenoid sinus.

An ectopic pituitary adenoma, exclusively involving the sphenoid sinus, associated with a normal size pituitary gland and an empty sella is a rare clinical entity. Only four cases have been found in the literature. We describe the case of a 47-year-old woman with clinical and biochemical acromegaly. Computed tomography (CT) appeared to show expansion of the sellar floor inferiorly into the sphenoid sinus, and magnetic resonance imaging (MRI) demonstrated an empty sella and a mass lesion confined to the sphenoid sinus. The tumor was totally resected by taking a transnasal endoscopic approach and the dura mater of the base of the pituitary fossa was confirmed intact.

Acromegaly↗

Acromegaly caused by growth hormone-relating hormone in a patient with multiple endocrine neoplasia type I.

A 51-year-old Caucasian man with multiple endocrine neoplasia (MEN) type I syndrome presented with clinical features of acromegaly. Exploration of the pituitary gland only revealed somatotrophic hyperplasia and his plasma growth hormone (GH) levels remained elevated. Production of growth hormone-releasing hormone (GHRH) by an ectopic tumor was suspected and, after additional investigations, a large pancreatic tumor was detected and removed. As the pancreatic tail contained multiple (occult) adenomas, lifelong follow-up was considered necessary. The patient has been recurrence-free for 10 years. All 19 living relatives of this patient were analysed for endocrine disorders related to MEN I syndrome. A brother was found to suffer from peptic ulcer disease caused by hyperparathyroidism and, during screening for other organ involvement associated with the MEN I syndrome, two tumors were found, one (4 cm) in the pancreatic tail region and one in the right adrenal gland. To date, six other family members have been found to suffer or have suffered from hyperparathyroidism and in a male subject, a prolactinoma and hyperparathyroidism were detected.

Acromegaly↗

Transgenic rabbits overexpressing growth hormone develop acromegaly and diabetes mellitus.

Transgenic rabbits expressing the bovine growth hormone (bGH) gene in liver and kidney were obtained to study the long-term effects of chronic exposure to GH in nonrodent animals. These rabbits presented high levels of bGH and insulin-like growth factor I in serum. In spite of chronic exposure to bGH, transgenic rabbits had similar body weight to controls. However, enlargement of the head and limbs and reduction of visceral fat were observed in these animals. They also showed marked hyperinsulinemia, hyperglycemia, and hypertriglyceridemia, indicating that they developed insulin resistance. Furthermore, serious histopathological alterations, including marked fibrosis, were observed in liver, kidney, and skeletal muscle. These anatomical, metabolic, and histological alterations closely resemble those found in patients with acromegaly. Thus, transgenic rabbits overexpressing GH may be a good model of the human disease.

Acromegaly↗

Ultrastructure of the skeletal muscles in acromegaly--before and after hypophysectomy.

Electron microscopic examination of the skeletal muscles in a patient with acromegaly and marked elevation of the serum growth hormone reveals altered mitochondria (pleomorphism, elongation, matrical pallor, and cristae abnormalities), glycogen granules infiltration, inclusion bodies, and vesicular dilatations. Nine months after surgical removal of the pituitary tumor, the serum growth hormone levels were markedly diminished. A repeat examination of the skeletal muscle shows that the previous ultrastructural changes in the muscles are related to the growth hormone levels.

Acromegaly↗

Kissing intrasellar carotid arteries in acromegaly: CT demonstration.

Acromegaly is a disease with protean manifestations that are well described in the literature. One finding infrequently encountered is aneurysmal dilatation of the internal carotid arteries and their branches. A case is presented, with CT documentation, in which the enlarged cavernous portions of the internal carotid arteries prolapsed into the sella turcica and enlarged it. Frontal bossing, frontal sinus enlargement, a dense cortical calvarium, prominent inion, and proptosis secondary to extraocular muscular enlargement were findings also present in this patient. The sella CT appearance has brought the term "kissing intrasellar arteries" to mind to suggest the diagnosis.

Acromegaly↗

Polyostotic fibrous dysplasia and acromegaly.

A review of the recent orthopaedic literature reveals little information on the endocrinopathic associations of polyostotic fibrous dysplasia. This article illustrates the need for endocrinologic evaluations at both initial diagnosis and at follow-up examinations. Two patients with polyostotic fibrous dysplasia and acromegaly are presented. In both cases, diagnosis was made by endocrinologic and radiographic evaluations, including computed tomography (CT) scan of the skull. One patient had pituitary macroadenoma, and the other had pituitary microadenoma. Irradiation therapy was performed successfully in both patients without any complications.

Acromegaly↗

Kidney function in acromegaly.

Creatinine clearance and daily urinary albumin and beta2-microglobulin excretion rates (radio-immunoassays) were measured several times in 14 patients with acromegaly. Eleven patients were treated with bromocriptine, 5 to 55 mg/day. The activity of the disease was assessed by measuring urinary growth hormone excretion (radio-immunoassay). In agreement with previous investigations we found the creatinine clearance elevated. However, no correlation was found between this variable and urinary growth hormone excretion. Urinary albumin and beta 2-microglobulin excretion rates were not significantly different from our previous results in 27 adults control subjects. There was no correlation between urinary growth hormone excretion and urinary albumin or beta 2-microglobulin excretion rates. Bromocriptine treatment reduced urinary growth hormone excretion from 220 to 91 ng/24 hours, p less than 0.01, but no significant alterations were induced in the above mentioned kidney function variables.

Acromegaly↗

Prolactin secretion in the empty sella syndrome, in prolactinomas and in acromegaly.

Prolactin (PRL) secretion was studied in 47 patients with empty sella syndrome. Hyperprolactinemia (39-123 micrograms/l) was found in six of them. Intermittent increases in PRL were noted in another seven patients. In most subjects with empty sella syndrome and hyperprolactinemia, diurnal PRL variation was altered or impaired whereas the PRL response to TRH and L-dopa was normal. Low doses of bromocriptine (3.75-5 mg/day) normalized PRL. In patients with prolactinoma and acromegaly who had prolactin levels of 30-165 micrograms/l the diurnal PRL variation and PRL response to TRH were impaired. Patients with prolactinoma failed to suppress PRL during L-dopa test. The dose of bromocriptine required to normalize PRL ranged between 7.5 and 15 mg/day. It is concluded that in subjects with sellar changes and intrasellar cisternal herniation ("empty sella"), and with moderate increases in PRL, the responses to TRH and L-dopa and to bromocriptine may help to differentiate between the empty sella syndrome and a coexisting pituitary tumour.

Acromegaly↗

Normal growth hormone secretion is rare after microsurgical normalization of growth hormone levels in acromegaly.

The effect of microsurgery on growth hormone (GH) secretion was studied in 34 patients with acromegaly. All patients showed enlarged sella volumes according to encephalography and macroadenomas at surgery. Preoperative GH levels were elevated in all 34 patients and 14 had concomitant hyperprolactinemia. There was a correlation between basal GH levels and sella size. Visual field defects, suprasellar extension, long duration of the disease, hyperprolactinemia and aneuploidy were noted in patients with low as well as high levels of GH preoperatively. The average reduction of GH levels in the total series was 71 +/- 21% (mean +/- SD). A notably similar reduction of GH levels was seen regardless of preoperative GH levels, concomitant hyperprolactinemia, visual field defects, size of the adenoma, invasive growth or increasing experience of the surgeon. Therefore, normal GH levels after surgery were reached mainly in patients with moderate GH increments preoperatively. GH levels were normalized by surgery in 15 patients but only four of these showed normal GH response to TRH and iota-dopa tests. Thus, only four patients (12%) fulfilled these criteria for cure of GH homeostasis.

Acromegaly↗

Epidemiology and long-term survival in acromegaly. A study of 166 cases diagnosed between 1955 and 1984.

In 1985, a follow-up investigation was performed of all patients with acromegaly (n = 166, 89 women and 77 men) seen over a 30-year period (1955-1984) at our Endocrine Unit, referral centre for the western region of Sweden (population 1.5 million). At the end of 1984, the prevalence of the disease was 6.9 per 10(5) inhabitants, the average incidence per year was 3.3 per million people. Mean age at diagnosis was 46.3 years and at death (n = 62) 64.1 years. About one-third of the patients (50/153), in whom it had been possible to estimate the total duration of the disease, had survived for more than 25 years. Mortality was, however, increased compared to the normal population. The observed number of deaths from vascular and malignant disorders was 32 and 15, respectively, compared to the expected numbers 9.0 (p less than 0.001) and 5.6 (p less than 0.01).

Acromegaly↗

Chondro-calcinosis and difficult intubation in acromegaly.

Difficulties encountered in carrying out tracheal intubation in acromegalic patients have been well documented. This paper reports the difficulty encountered in a patient with acromegaly complicated by extensive calcification of the larynx.

Acromegaly↗

Effects of nomifensine, an inhibitor of endogenous catecholamine re-uptake, in acromegaly, in hyperprolactinaemia, and against stimulated prolactin release in man.

1. Nomifensine, an inhibitor of endogenous catecholamine re-uptake, did not affect the growth hormone (GH) or prolactin levels in patients with acromegaly or hyperprolactinaemia. It does not, therefore, have any therapeutic role in these conditions at the dosage used in this study. 2. It had no effect on thyrotrophin-releasing hormone (TRH)-induced thyrotrophin (TSH) or prolactin release in males, yet caused marked suppression of monoiodotyrosine (MIT)-induced prolactin release in males but not in females. 3. The significant suppression of MIT-induced prolactin release in males is likely to reflect the dopamine (DA) agonist activity of the drug and its lack of effect in the other situations tested could be dose related. 4. It is proposed that the difference in male and female patterns of prolactin response to MIT after nomifensine, could be due to a "damping" effect of oestrogen on the hypothalamic dopaminergic system.

Acromegaly↗

Treatment of acromegaly by transsphenoidal hypophysectomy with cryoapplication.

The therapeutic effect of transsphenoidal hypophysectomy with cryoapplication has been studied in twenty-nine patients with active acromegaly. The mean follow-up time was 15 months (354 months). A significant improvement of symptoms and signs occurred in all but three patients. The level of plasma immunoreactive growth hormone (IRGH) was reduced in all but two patients and a normal level of plasma IRGH was achieved in sixteen patients. Skin thickness, the level of serum inorganic phosphorus and the urinary excretion of hydroxyproline and calcium were significantly decreased in the great majority of the patients. The operation was not accompanied by any visual complications, but cerebrospinal rhinorrhoea, subsiding spontaneously, developed in two and postoperative meningitis in one patient. Hypothyroidism and adrenocortical deficiency developed in eight, gonadotrophin deficiency in thirteen, and persistent diabetes insipidus in one patient. It is concluded that transsphenoidal hypophysectomy with cryapplication is a safe and effective method for the treatment of acromegalic patients.

Acromegaly↗

Acromegaly caused by pulmonary carcinoid tumours.

Two patients are described whose acromegaly was cured by removal of a bronchial carcinoid tumour. One had an enlarged pituitary fossa and evidence is presented that in this patient the tumour was not secreting growth hormone. The evidence available suggests that the tumour was producing a growth hormone releasing substance. It is suggested that some cases of the pluriglandular syndrome may be secondary to small bronchial carcinoid tumours that produce substances as yet unidentified, that stimulate the growth and hyperactivity of other endocrine tissue.

Acromegaly↗