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Dopamine agonists are effective in some patients with acromegaly and in this condition treatment is considered to be chronic. We describe two acromegalic patients who responded adequately to the long-acting dopamine agonist cabergoline, but surprisingly maintained normal GH and IGF-I levels once therapy was discontinued after 42 and 76 months because of possibly related side effects. A 32-year-old woman with mild acromegaly (IGF-I: 423 microg/l, GH after OGTT: 2.5 microg/l, adenoma 4 mm) was treated with cabergoline as primary therapy and reached safe GH levels (2 microg/l or less) and normal IGF-I levels with 3.5 mg cabergoline weekly. After 42 months of therapy the patient experienced a progressive decrease of libido, which she attributed to the intake of cabergoline. After stopping medication, serum levels of GH and IGF-I remained normal during the following 2.5 years. A 53-year-old man with moderate acromegaly (serum IGF-I: 547 microg/l, GH after OGTT: 5.9 microg/l, adenoma 7 mm) preferred cabergoline as primary therapy. Serum GH levels below 2 microg/l and normal levels of IGF-I were obtained with 3.5 mg cabergoline weekly. When the patient experienced severe stomach pains after 76 months of treatment, cabergoline was held responsible and discontinued. Serum GH and IGF-I did not increase again and stayed at the same level during a follow-up of 5.5 years. These two cases demonstrate that acromegalic patients with a good response to cabergoline may occasionally remain in remission after stopping therapy. This phenomenon has previously only been described in patients with a prolactinoma.

Background: Cushing's syndrome is a rare disorder. The corticotropin (ACTH)-dependent form of this syndrome generally results either from excessive ACTH secretion by a pituitary adenoma or ectopic secretion by a malignant tumor. Theoretically, the latter type can be assumed to occur more frequently in old age as the incidence of malignancy increases., Methods: Diagnostic procedures for these five cases of Cushing's syndrome consisted of 24-hour urinary cortisol excretion, plasma ACTH and serum cortisol levels, oCRH stimulatory test, low-dose and high-dose dexamethasone suppression tests, CT scan or MR imaging of the pituitary region, and bilateral inferior petrosal sinus sampling. Patients were treated with ketoconazole, if possible, and evaluated according to clinical response and 24-hour urinary cortisol excretion., Patients: The five cases presented were selected on the basis of age--75 years or older--from a total of about 100 patients presenting with Cushing's syndrome. In only three cases were signs of hypercorticism found on clinical examination. The other two patients were evaluated for adrenocortical excess because of severe hypokalemia and the fortuitous finding of enlarged adrenal glands on CT scan, respectively., Results: As a result of endocrine testing, pituitary-dependent Cushing's disease was suspected in three patients and ectopic Cushing's syndrome in two patients. Imaging techniques demonstrated only one pituitary adenoma in the first three patients and a lung tumor in one of the latter two patients. Inferior petrosal sinus sampling confirmed the suspected origin of the Cushing's syndrome in the three patients in which this procedure was performed. All three patients with pituitary-dependent Cushing's disease underwent successful clinical and biochemical treatment with ketoconazole., Conclusion: Pituitary-dependent Cushing's disease may occur more frequently in patients older than 75 years of age than has previously been assumed. Because surgical treatment is not always easily tolerated by older patients, the steroidogenesis inhibitor, ketoconazole, can be a valuable alternative for the control of hypercorticism.

Angioimmunoblastic lymphadenopathy is a rare lymphoproliferative disease with a poor prognosis. We saw a 24-year-old female patient with a fulminant evolution of an angioimmunoblastic lymphadenopathy, possibly a recurrence after a 10 years remission.

Quinagolide (CV 205-502, Sandoz), an octahydrobenzo (g) quinoline, is a new non-ergot dopamine agonist which has specific D2 receptor activity and a long half-life, making it suitable for once-daily treatment. Recent uncontrolled reports have suggested that quinagolide may be successfully used for the clinical management of hyperprolactinemia with fewer adverse reactions than bromocriptine. This study is the first to compare quinagolide in a double-blind manner with bromocriptine, given only once-daily instead of the usual multidose regimen. In the first phase we compared, in 7 hyperprolactinemic patients, the effects over 24 h of a single oral dose of 0.05 mg quinagolide with 2.5 mg bromocriptine. Compared with placebo, both bromocriptine and quinagolide showed potent PRL-inhibiting and GH-releasing effects, with comparable effects at 24 h; no significant changes were observed in TSH, LH, FSH or cortisol. Twelve hyperprolactinemic patients were then randomized to receive either once-daily bromocriptine or quinagolide in incremental doses for a period of six months. Both drugs were found to be equally effective, and no differences were seen either in adverse reactions or PRL levels during repeated diurnal sampling. We therefore conclude that quinagolide and bromocriptine are therapeutically equivalent in long-term use, and both are equally effective when given once a day. However, some patients intolerant of bromocriptine may respond better to quinagolide, and vice versa.

Objective: To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome., Design: An evaluation of the standard clinical practice at one institution., Patients: Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome., Measurements: The acute response to metyrapone was assessed by measuring cortisol, 11-desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer-term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean., Results: A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours in all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11-desoxycortisol levels increased in all patients, while plasma ACTH increased in patients with pituitary Cushing's disease and the ectopic ACTH-syndrome. Fifty-three patients with Cushing's disease were followed on short-term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408-2240) dropped to the target range of less than 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750-6000). Metyrapone was given long term in 24 patients with Cushing's disease who had been given pituitary irradiation, for a median of 27 months (range 3-140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750-6000) reduced their mean cortisol levels (median 847 nmol/l, range 408-2000) to less than 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH-syndrome the 'mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823-6354) were reduced to less than 400 nmol/l in 13 patients (70%), on a median dose of 4000 mg/day (range 1000-6000). Reduction of cortisol levels was clearly associated with clinical and biochemical improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side-effects., Conclusions: In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.

Ketoconazole, an oral antimycotic agent, is known to have a potent inhibitory effect on adrenal steroid production. It was given at a dose of 1200 mg/day to a 52-year-old female patient with a virilizing adrenocortical carcinoma in order to achieve better metabolic control pre-operatively. Together with a rapid normalisation of hypertension and hyperglycemia, a dramatic fall was noticed in serum and urinary adrenal steroids after a few days. Levels of total testosterone (20 nmol/l), androstenedione (greater than 35 nmol/l) and DHEA-sulphate (greater than 28 nmol/l) fell to normal levels in 6 days. By contrast, levels of 17-OH-progesterone (30 nmol/l) and progesterone (2.45 nmol/l) increased slightly, indicating inhibition of adrenal 17,20-lyase. Cortisol (620 nmol/l at 08.00 h) fell to very low levels (50 nmol/l) on day 6 of the trial. We conclude that ketoconazole is very effective in suppression of adrenal tumoural steroidogenesis and merits consideration in pre-operative use. We warn against dangerous hypoadrenalism which seems to occur earlier in tumoural than in normal adrenal metabolism.

In a 47-year-old patient with renovascular hypertension due to a totally obstructed left and a severe constricted right renal artery, a successful transluminal renal angioplasty was performed with normalisation of blood pressure. Thirteen days later the patient died of a mesenteric infarction, possibly caused by normalisation of the blood pressure in the presence of a severe mesenterical stenosis. The benefit of preventive screening of other vital organs in highly atheromatous patients is discussed.

With the conventional, discrete RAST various tests are required to detect IgE of different specificities in the same serum. To overcome this problem and to reduce the costs, a multiple RAST with seven different mixtures was compared with the individual mixture constituents and with the 12 individual allergens currently in use in our department. One grass pollen mixture (gx3), two weed pollen mixtures (wx3, wx4), two tree pollen mixtures (tx5, tx6), one mould mixture (mx1) and one epithelial mixture (ex1) were used. A mixture of mites was not evaluated as there is only one important pathogenic organism in our regions (Dermatophagoides pteronyssinus or House dust mite). For grasses the gx3 mixture offered no advantage over the discrete RAST. The weed mixture wx3 was more sensitive than the most common discrete RAST's but at the cost of specificity. The wx4 mixture should not be used because the specificity is too low. The tree mixtures were not significantly more sensitive than the most common individual tree allergens, and were less specific. Mould mixtures should not be used because there is little cross-reactivity between the individual allergens, thus using a mixture would necessitate the subsequent determination of individual allergens, and the number of tests and the cost would be even higher. Neither should a mixture be used for epithelia because one wants to detect allergies to individual allergens. Moreover, the sensitivity of the epithelial mixture was too low. In general, we suggest the use of a limited panel of discrete RAST's instead of mixtures.

A 48-year-old diabetic patient was admitted to hospital with fever and extensive infection of the tissues around the right elbow. Diagnosis was made of cellulitis and underlying osteomyelitis caused by Streptococcus pneumoniae. Although seen in patients with seriously impaired host defence mechanisms pneumococcal osteomyelitis and cellulitis has not been reported in a diabetic patient.

Forty-three patients with type I allergic respiratory diseases received aqueous grass pollen immunotherapy in a prospective study designed to compare the clinical and biological effects of a semi-rush hyposensitization (20 patients) with ordinary hyposensitization (23 patients). Before the start of the therapy (end of previous grass pollen season, t1) and before (t2) and after the next grass pollen season (t3), total serum IgE (tIgE), grass pollen-specific IgE (GPsIgE), grass pollen-specific IgG (GPsIgG) and complement factors C3 and C4 were determined. GPsIgE and GPsIgG levels increased significantly more during immunotherapy in patients receiving the semi-rush scheme as compared with the ordinary scheme. There were no significant changes between the two schemes at any times for tIgE, C3 and C4. GPsIgG was already higher in allergic patients before the start of therapy as compared with non-allergic patients and controls. Clinical improvement was the same in patients treated with the semi-rush scheme as in the ordinary group. The number of side effects was not statistically different between the two groups. In neither group was there a correlation between the change in biological parameters and change in clinical symptoms. As the semi-rush scheme gives the same results immunologically as well as clinically, it could be used in a number of patients since it reduces the time course of the initial therapy by about 2 months.

A case is presented of a 26-year-old male with a 8-day history of fever and back pain, and limb weakness beginning 24 hours before admission. An abscess caused by a staphylococcus aureus was localised in the thoracic paravertebral region with penetration in the subarachnoidal space at T1. Myelography appeared to be superior to CAT-scan and NMRI of the cervico-thoracal region in supporting the diagnosis. Treatment by laminectomy of C7-T3 48 hours after admission did not lead to neurological improvement and an incomplete tetraplegia persisted. The importance and difficulty of early diagnosis is stressed.