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Biomedical subjects

W Arlt

Publications and source records attributed to W Arlt.

43 records · Page 3Linked to original sources
PubMed1997

Frequent and frequently overlooked: treatment-induced endocrine dysfunction in adult long-term survivors of primary brain tumors.

New treatments for primary brain tumors have improved survival but quality of life may be impaired by neuroendocrine dysfunction. We performed a controlled, cross-sectional study to assess frequency and clinical impact of endocrine dysfunction in adult long-term survivors of primary brain tumors outside the hypothalamic-pituitary region. Thirty-one patients (19 males and 12 females; age, 25 to 66 years) and 31 sex- and age-matched controls were studied 1.5 to 11 years after radiotherapy with a mean total dose of 62.3 +/- 2.8 Gy (mean local doses pituitary, 51.1 +/- 12.1 Gy; hypothalamus, 57.0 +/- 7.8 Gy). Structured clinical assessment included a standardized questionnaire. Thyroid, adrenal, and gonadal hormones were measured at baseline and, in the patients, also after stimulation. Sixteen patients (52%) reported two or more symptoms suggestive of hypothyroidism; eight patients (26%) showed evidence of hypothalamic hypothyroidism. Patients had significantly lower serum baseline concentrations of cortisol and dehydroepiandrosterone sulfate than controls, but no manifest hypoadrenalism was noticed except in one patient with panhypopituitarism. Forty-seven percent of the male patients, but only six percent of the controls, suffered from erectile dysfunction; 42% of the male patients showed either evidence of hypothalamic hypogonadism (32%) or primary gonadal damage (10%). Nine patients (29%) presented with hyperprolactinemia and four women concurrently suffered from oligo-amenorrhea. In adult patients treated for primary brain tumors, endocrine dysfunction due to radiation-induced hypothalamic damage is common and has a significant impact on well being. Endocrinologic evaluation should be performed periodically in these patients.

Adrenal Glands↗
PubMed1994

Suramin in adrenocortical cancer: limited efficacy and serious toxicity.

OBJECTIVE: No satisfactory treatment for adrenocortical carcinoma (ACC) is available. We investigated the efficacy and toxicity of suramin in the treatment of metastatic ACC since suramin has been recently reported to be active as a single agent therapy for patients with ACC and prostatic carcinoma. DESIGN: We collected data on 9 patients with metastatic ACC treated with suramin in four centres in Germany between 1987 and 1992. PATIENTS: Nine patients (5 women, 4 men; age range 32-67 years) were included. Biochemical evidence of steroid excess was found in 6/9, in three leading to clinical symptoms (hypertension, hyperglycaemia, hirsutism, gynaecomastia). MEASUREMENTS: Tumour responses were assessed by radiological and biochemical evaluation. Other investigations included regular measurements of blood cell counts, coagulation, hepatic and renal function parameters, and serum suramin concentrations. RESULTS: The patients received cumulative doses ranging from 8.2 to 30.2 g suramin over periods of 1-15 months. 3/9 achieved a partial response, 2/9 disease stabilization and 4/9 experienced progressive disease. Tumour responses were transient. Suramin treatment was without direct influence on steroid excess. Serious side-effects included coagulopathy (6/9), thrombocytopenia (6/9), polyneuropathy (2/9) and allergic skin reactions (4/9); the death of two patients was possibly related to suramin therapy. Both toxicity and tumour response were strongly associated with serum level or cumulative dose of suramin. CONCLUSIONS: (1) Suramin is of antineoplastic efficacy in the treatment of metastatic adrenocortical carcinoma. (2) The clinical use of suramin is limited by a narrow therapeutic window with the risk of serious and possibly lethal toxicity at one extreme, and loss of efficacy at the other. Strict monitoring of suramin serum levels is mandatory aiming at levels between 200 and 250 mg/l. Suramin should not be considered as first-line treatment for metastatic adrenocortical carcinoma. (3) To improve treatment options in adrenocortical carcinoma as well as for further investigation on the usefulness of suramin, controlled prospective trials are urgently needed.

Adrenal Cortex Neoplasms↗
PubMed1994

Impairment of adrenocortical function associated with increased plasma tumor necrosis factor-alpha and interleukin-6 concentrations in African trypanosomiasis.

African sleeping sickness (SS) is a severe, potentially lethal parasitic disease. The treatments of choice are the antiparasitic agents suramin, which is adrenotoxic, and/or melarsoprol. We evaluated the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis of patients with SS before, during, and after therapy with suramin and/or melarsoprol, in two sequential stages. First, we employed the standard adrenocorticotropic hormone (ACTH) 1-24 stimulation test (250 micrograms i.v.) to assess the maximal adrenocortical responsiveness of 69 patients with SS and 38 normal controls. We demonstrated paradoxically subnormal cortisol responses before suramin therapy [net cortisol response 60 min after stimulation: 10.5 +/- 2.9 (mean +/- SE) vs. 17.5 +/- 1.0 micrograms/dl for controls, p = 0.004], with 27% of the patients falling within the adrenal insufficiency range (stimulated cortisol concentration < 20 micrograms/dl). These responses subsequently and unexpectedly improved with suramin and/or melarsoprol therapy. Second, we performed a human corticotropin-releasing hormone (hCRH) test (100 micrograms i.v.) in 68 additional patients with SS and 14 control subjects to examine whether the glucocorticoid deficiency observed was primary and/or secondary. Compared to controls, the ACTH and cortisol responses to hCRH were blunted (ACTH after 60 min: 29 +/- 7 vs. 58 +/- 8 pg/ml in controls, p = 0.014; cortisol: 15.2 +/- 1.5 vs. 19.6 +/- 0.7 micrograms/dl, p = 0.018), suggesting the presence of secondary adrenal insufficiency. There was improvement of both ACTH and cortisol responsiveness to hCRH with therapy, with cortisol recovery occurring before ACTH, suggesting an additional primary component of adrenal dysfunction in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Treatment of metastatic adrenal carcinoma with suramin].

A right adrenocortical carcinoma (weighing 978 g) was removed from a 45-year-old man in April 1986, the tumour bed then being irradiated with 40 Gy. Subsequently discovered multiple lung metastases were treated with cisplatin, etoposide and bleomycin, without improvement. Treatment with mitotane (Lysodren) was also without effect and had to be discontinued because of severe side effects. Treatment with suramin (Germanin) was begun in August 1987. After a loading dose of 10.7 g for six weeks the lung metastases regressed almost completely. But lung metastases were again demonstrated in January 1988 during a low-dose maintenance regimen of suramin. Increased dosage arrested further growth, but achieved no regression of the metastases. The patient died unexpectedly in April 1988 of acute circulatory failure. Suramin administration had been discontinued six weeks earlier because of bronchopneumonia and general deterioration. Thrombocytopenia, coagulation disorders and moderate proteinuria were the side effects of suramin treatment.

Adrenal Cortex Neoplasms↗
PubMedDate not supplied

Adrenocortical insufficiency in Rhodesian sleeping sickness is not attributable to suramin.

Suramin, a polysulphonated naphthylurea used in the treatment of human African trypanosomiasis (HAT), is known to cause adrenocortical insufficiency in doses exceeding the quantity used for treatment of HAT. We have previously reported that Trypanosoma brucei rhodesinese infection causes a combined central and peripheral adrenal insufficiency. To evaluate whether suramin therapy acts as an additional adrenotoxic factor, we assessed adrenocortical function in 72 patients suffering from HAT at different times during treatment with either suramin or melarsoprol by a rapid adrenocorticotropic hormone test. We found a significantly diminished peak cortisol response to stimulation in the acutely ill patients (P = 0.001), indicating impaired adrenocortical function, as well as a high incidence of partial adrenocortical insufficiency (27%). During and after trypanocidal therapy the incidence of partial adrenal insufficiency gradually declined (to 25% and 18% respectively). Stimulated peak cortisol levels did not differ significantly between patients receiving suramin and those given melarsoprol. No correlation was found between serum suramin concentration and the cortisol response to stimulation (r = 0.09, P = 0.47). Thus we conclude that suramin in trypanocidal doses neither causes nor worsens the adrenocortical dysfunction observed in Rhodesian HAT.

Addison Disease↗