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Biomedical subjects

M Reincke

Publications and source records attributed to M Reincke.

At least 109 records · Page 6Linked to original sources
PubMed1994

[Surgical interventions of the adrenal gland. Diagnosis and results of treatment].

From 1982 to 1992, 33 patients underwent adrenalectomy for disease of the adrenal gland: 18 patients with adrenal cortex adenoma or hyperplasia (Cushing's syndrome n = 11, Conn's syndrome n = 6, adrenogenital syndrome n = 1), 3 with pituitary-dependent Cushing's disease, 7 with pheochromocytoma (malignant n = 1), 2 with a metastasis of lung cancer and 1 with cystic adrenal necrosis. Multiple endocrine neoplasia existed in four cases. Various preoperative symptoms were noted, including complaints typical of the respective syndromes and general abdominal symptoms. Other patients were symptom-free with incidental findings. An intercostal approach was used in 30 cases, a transabdominal approach in 3 cases. In 6 cases bilateral and in 27 cases unilateral adrenalectomy was performed. In two cases additional nephrectomy became necessary because of extensive adhesions. Intraoperatively, one patient suffered a blood pressure crisis. 31 patients are still alive and symptom-free after a mean follow-up of 5.4 years (range 1-11 years). Two patients have died (one with benign pheochromocytoma and one with a metastasis of lung cancer). Detailed preoperative hormone analysis and adequate preoperative medication substantially lowers the risk involved in adrenal surgery. However, the indications for surgical treatment of hormonally inactive, symptom-free adrenal tumors that are found incidentally remain controversial, and surgery should perhaps be restricted to large tumors.

Adolescent↗
PubMed1993

Thyroid dysfunction in African trypanosomiasis: a possible role for inflammatory cytokines.

OBJECTIVE: Sleeping sickness (African trypanosomiasis) is an anthropozoonosis transmitted by the tsetse fly. The treatments of choice are the antiparasitic agents suramin and/or melarsoprol. Experimental infection of animals with Trypanosoma brucei results in inflammatory lesions in the pituitary and/or the thyroid gland. In biochemical terms, these animals have hypothyroidism. We evaluated the functional integrity of the hypothalamic-pituitary-thyroid axis in patients with African trypanosomiasis before, during and after specific therapy. DESIGN: Prospective, controlled, cross-sectional study. PATIENTS AND MEASUREMENTS: Sixty-five patients with sleeping sickness (31 female, 34 male; aged 18-66; 32 with haemolymphatic sleeping sickness receiving suramin i.v., 33 with cerebral sleeping sickness receiving melarsoprol) and 13 control subjects (6 female, 7 male; aged 21-60) were enrolled in a cross-sectional study after giving informed consent. Fourteen patients were studied shortly after admission for sleeping sickness, 19 in the middle of the course of treatment, 18 at the end of the 5-week treatment period, and 14 patients after cure. All subjects underwent a TRH stimulation test at 1200 with bolus injection of 400 micrograms TRH i.v. Blood was drawn for determination of fT3, fT4, TSH, rT3, TNF-alpha, IL-1 and IL-6 at 0 minutes and TSH at 60 minutes. All hormones and cytokines were determined by RIA or ELISA. RESULTS: Baseline TSH concentrations (mean +/- SEM) were elevated in unmedicated patients with sleeping sickness compared to normal subjects (2.6 +/- 0.4 vs 1.4 +/- 0.2 mU/l; P = 0.01), whereas fT3 (2.7 +/- 0.5 vs 5.8 +/- 0.3 pmol/l; P = 0.0002) and fT4 concentrations (10.3 +/- 1.2 vs 15.4 + 0.8 pmol/l; P = 0.007) were low. Stimulated TSH concentrations did not significantly differ from normal controls. Reverse T3 concentration in patients with sleeping sickness were normal (2.2 +/- 0.3 vs 2.4 +/- 0.2 nmol/l; P = NS). During the course of treatment, baseline TSH, fT3 and fT4 concentrations slowly returned to normal and were indistinguishable from controls after cure. Plasma concentrations of TNF-alpha (16.0 +/- 4.1 vs 2.9 +/- 1.4 ng/l in controls; P = 0.003) and interleukin-6 (19.2 +/- 7.3 vs 1.3 +/- 0.2 ng/l; P = 0.0001), but not interleukin-1 beta (2.0 +/- 0.2 vs 0.9 +/- 0.2, ng/l P = NS), were elevated, when thyroid function impairment and disease activity were at their maximum, but gradually decreased into the normal range with therapy. We found a negative correlation between baseline cytokine concentrations and fT3 concentrations (TNF-alpha: r = -0.34, P = 0.003; IL-6: r = -0.43, P = 0.0001). CONCLUSIONS: We conclude that unmedicated sleeping sickness is associated with significant impairment of thyroid function, which is reversed with specific therapy. Elevated TSH concentrations and low fT3 and fT4 concentrations suggest primary hypothyroidism in patients with sleeping sickness. However, an additional pituitary and/or hypothalamic component cannot be excluded. This impairment may be due to the elevated plasma cytokine concentrations found in these patients or may be the result of parasitic thyroiditis.

Adolescent↗
PubMed1993

The hypothalamic-pituitary-adrenal axis in critical illness: response to dexamethasone and corticotropin-releasing hormone.

Plasma ACTH and cortisol concentrations are frequently elevated in patients in intensive care units (ICU). To examine the functional integrity of the hypothalamic-pituitary-adrenal axis during critical illness, we evaluated prospectively 53 ICU patients in a general medical ICU. Thirty-one patients and 7 normal controls underwent an overnight dexamethasone suppression test (3 mg dexamethasone, orally, at 2300 h). Plasma ACTH and serum cortisol were measured at 0900 h. In a separate experiment, 22 patients and 7 control subjects underwent a CRH stimulation test [100 micrograms human (h) CRH, iv]. ACTH and cortisol concentrations were determined from -15 to 120 min. Compared to normal controls, plasma ACTH and serum cortisol concentrations were not fully suppressible by dexamethasone [mean +/- SEM: plasma ACTH, 21 +/- 4 vs. 3 +/- 0.5 pg/mL (4.7 +/- 0.9 vs. 0.7 +/- 0.1 pmol/L); serum cortisol, 13.9 +/- 1.9 vs. 1.5 +/- 0.3 micrograms/dL (390 +/- 50 vs. 40 +/- 10 nmol/L); P = 0.0001], demonstrating an altered glucocorticoid feedback in the ICU patients. Patients undergoing hCRH stimulation had clearly elevated mean baseline plasma ACTH and serum cortisol concentrations [ACTH, 78 +/- 20 pg/mL vs. 15 +/- 3 in controls (17.2 +/- 4.4 vs. 3.4 +/- 0.7 pmol/L; P = 0.007); cortisol, 36.8 +/- 3.4 micrograms/dL vs. 9.6 +/- 1.2 (1020 +/- 80 vs. 260 +/- 30 nmol/L; P = 0.0001)]. Despite elevated baseline glucocorticoid concentrations, stimulation with hCRH resulted in significantly higher peak plasma ACTH concentrations 15 min after hCRH than in controls [134 +/- 31 vs. 48 +/- 9 pg/mL (29.5 +/- 6.8 vs. 10.6 +/- 2.0 pmol/L); P < 0.05]. Serum cortisol concentrations in ICU patients were significantly elevated throughout the test period (P = 0.0001) and rose to a peak of 43.9 +/- 3.5 micrograms/dL compared to 18.2 +/- 2.0 micrograms/dL in controls (1210 +/- 70 vs. 500 +/- 60 nmol/L). We conclude that ICU patients have a markedly altered responsiveness of their pituitary corticotroph to suppression with dexamethasone and stimulation with hCRH. These findings may be explained by altered pituitary glucocorticoid feedback and/or hypersecretion of peptides with CRH-like activity (vasopressin and cytokines) during critical illness.

Adrenal Glands↗
PubMed1993

No evidence for oncogenic mutations in guanine nucleotide-binding proteins of human adrenocortical neoplasms.

G-Proteins are membrane-bound heterotrimeric polypeptides that couple receptor signals to second messenger systems such as cAMP. Recently, point mutations at 2 codons of the highly preserved alpha-chain of Gs, the adenyl cyclase-stimulating G-protein, were found in GH-secreting pituitary tumors. These mutations resulted in constitutively activated Gs alpha and high intracellular cAMP levels. In addition, point mutations at similar codons of a different G-protein, G(i) alpha 2, were reported in adrenocortical neoplasms, suggesting a potential role of this isoform in the genesis of these tumors. We reevaluated the frequency of constitutively activating point mutations in the alpha-chain of the stimulatory (Gs alpha) and inhibitory (G(i) alpha 2) G-proteins in human adrenocortical tumors. Seven adrenocortical carcinomas, 2 human adrenocortical tumor cell lines, and 11 adrenocortical adenomas were studied. Genomic DNA was purified from either frozen tumor tissue or paraffin-embedded sections. Using specific primers and the polymerase chain reaction, DNA fragments surrounding codons 201 and 227 (Gs alpha) and 179 and 205 (G(i) alpha 2) were amplified and visualized on a 2% agarose gel. In a second asymmetric polymerase chain reaction, using nested primers, single stranded DNA was generated using 1-10 microL of the initial amplification mixture and directly sequenced using the dideoxy chain termination method of Sanger. We found no mutations at codons 201, 227 and 179, 205 of Gs alpha and G(i) alpha 2, respectively, in the tumors studied. We conclude that previously identified oncogenic point mutations in the stimulatory and inhibitory alpha-chain of G-proteins do not appear to be present at high frequency in adrenal neoplasms. Thus, the mechanism(s) of tumorigenesis in these tumors is different from that in GH-secreting adenomas and may involve oncogenic mutations of other cell constituents.

Adolescent↗
PubMed1993

[Magnetomyography with the SQUID].

The results of investigations of the neuromuscular system in man using a SQUID magnetometer with a second-order gradiometer detector are presented. After electrical stimulation of the tibial nerve in the hollow of the knee and the triggering of a monosynaptic proprioceptic reflex (Hoffmann-(H-)reflex), the biomagnetic field was recorded from the dorsal surface of the lower leg (soleus muscle of the m. triceps surae). The results obtained indicate that, over and beyond the data provided by electromyography, diagnostic information is provided on the state of the neuronal reflex pathways including muscle effector function. The biomagnetic field was evaluated in terms of latency, intensity, composition, characteristic behaviour and site of generation of the signal. In the geometry used, this noninvasive measuring technique can be employed for office observation of the spread of excitation through the muscle, as demonstrated by the response obtained following supramaximal stimulation of the supply nerve.

Electric Stimulation↗
PubMed1993

[Ectopic ACTH- or CRH-secreting tumors in Cushing's syndrome].

A collection of 13 tumors causing an ectopic Cushing's syndrome was composed of four bronchial carcinoids, one small cell carcinoma of the bronchus, one thymic carcinoid, two islet cell tumors of the pancreas, one pheochromocytoma, two medullary carcinomas of the thyroid, one prostatic cancer and one intrasellar choristoma. By immunohistochemistry, ACTH in combination with CRH was found in one bronchial carcinoid and in one islet cell carcinoma. ACTH but not CRH was demonstrable in one bronchial carcinoid, in both medullary carcinomas of the thyroid, in the thymic carcinoid and in the pheochromocytoma. CRH without ACTH was present in the small cell carcinoma of the bronchus, one bronchial carcinoid, the prostatic cancer and the choristoma of the sellar region. Neither ACTH nor CRH could be found in one islet cell carcinoma. In the pituitary (n = 7) Crooke's cells were found except in one case with islet cell carcinoma which was treated with adrenostatic drugs. The pituitary besides the intrasellar choristoma harbored an ACTH cell adenoma. The pathophysiological correlations are discussed.

Adenoma, Islet Cell↗
PubMed1992

Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome.

Adrenal tumors are usually diagnosed by clinical symptoms of hormone excess. The increasing use of ultrasound and computed tomography results in the detection of a substantial number of incidentally discovered adrenal tumors. Most of these tumors are nonfunctional adrenocortical adenomas, but a few cases of subclinical cortisol production in "incidentalomas" have been reported. We investigated prospectively the prevalence of autonomous cortisol production in 68 patients (44 females and 24 males, aged 25-90 yr) with adrenal incidentalomas at our institution. As a screening procedure all patients with incidentalomas underwent an overnight dexamethasone suppression test (1 mg). Patients who failed to suppress serum cortisol below 140 nmol/L (5 micrograms/dL) underwent more comprehensive studies (prolonged dexamethasone suppression test, determination of the diurnal rhythm of cortisol secretion in saliva, and CRH stimulation test). Eight patients (12% of all patients with incidentalomas; 5 females and 3 males, aged 25-71 yr) were finally identified as having cortisol-producing tumors, and the findings in these patients were compared with those of overt Cushing's syndrome in 8 patients (8 females, aged 26-50 yr) suffering from cortisol-producing adrenal adenomas. The tumor size of patients with cortisol-producing incidentalomas ranged from 2-5 cm. No specific signs and symptoms of hypercortisolism were present, but arterial hypertension (seven of eight subjects), diffuse obesity (four of eight subjects), and noninsulin-dependent diabetes mellitus (NIDDM; two of eight subjects) were frequently observed. Baseline cortisol levels were in the normal to upper normal range, whereas baseline ACTH levels were suppressed in five of the eight patients. In none of the patients was serum cortisol suppressible by low dose or high dose dexamethasone. The ACTH and cortisol responses to CRH were normal in two, blunted in one, and suppressed in four patients. Unilateral adrenalectomy was performed in seven patients and resulted in temporary adrenal insufficiency in four of them. After surgery, improvement of arterial hypertension, a permanent weight loss in obese subjects, and a better metabolic control of NIDDM were noted in the majority of patients. The following conclusions were reached. Incidentally diagnosed adrenal tumors with pathological cortisol secretion in otherwise clinically asymptomatic patients are more frequently observed than previously assumed. Adrenocortical insufficiency is a major risk in these patients after adrenalectomy. After surgery, hypertension, obesity, and NIDDM may improve. Patients with asymptomatic adrenal incidentalomas, therefore, should be screened for cortisol production by means of an overnight dexamethasone suppression test.

Adrenal Gland Neoplasms↗
PubMed1989

Gel chromatographic characterization of immunoreactive adrenocorticotropin in patients with ACTH hypersecretion.

We investigated the molecular size of circulating immunoreactive ACTH by gel chromatography in patients with ACTH hypersecretion due to various disorders of the hypothalamic-pituitary-adrenal axis. 4 patients with Addison's disease, 2 with Nelson's syndrome, 4 with Cushing's disease, 6 with the ectopic ACTH syndrome (2 bronchial carcinoma, 1 medullary carcinoma, 1 metastatic islett cell carcinoma, 1 benign bronchial carcinoid and 1 patient with occult ectopic Cushing's syndrome) and 1 patient with hypersecretion of ACTH from a clinically nonfunctioning pituitary adenoma were studied. Analysis of the molecular size of immunoreactive ACTH was performed by gel chromatography on a Sephadex G-75 column (superfine, 100 x 1.5 cm) equilibrated with 1% formic acid. 2 ml fractions were collected and evaporated to dryness. The ACTH content of the recovered samples was determined by RIA. In Addison's disease, Nelson's syndrome and Cushing's disease the plasma showed a single peak of ACTH immunoreactivity at the expected position of 1-39 ACTH. In the ectopic ACTH syndrome the plasma of 4 patients revealed at chromatography at least one other peak eluting between the void volume and 1-39 ACTH suggestive of a high molecular weight form of ACTH whereas plasma of 2 patients showed only a single ACTH peak at the position of labeled 1-39 ACTH. The patient with a clinically non-functioning pituitary adenoma revealed a gel filtration pattern similar to the patients with ectopic ACTH syndrome and secretion of high molecular weight ACTH. We conclude that secretion of high molecular weight forms of ACTH is not a unique feature of the ectopic ACTH syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

ACTH Syndrome, Ectopic↗
PubMed1989

[Diagnosis and therapy of asymptomatic adrenal tumors].

Adrenal tumours had been discovered incidentally (since 1981) in 32 patients (23 females and nine males; mean age 54 [25-73] years) who had had computed tomography (CT) or ultrasonography for other reasons: none had a history or symptoms of such tumour. Tumours were bilateral in eight, right or left-sided in 12 each: all had been confirmed by CT. Average tumour size was 3 cm (1-9 cm). Three patients had cortisol-producing adrenal tumours, and there was one benign phaeochromocytoma (abnormally high adrenaline and noradrenaline excretion). Fine-needle biopsies in two patients revealed a benign histology. An adrenalectomy was performed in eight patients (the one phaeochromocytoma, six adenomas and one ganglioneuroma). Follow-up CT in 11 of the non-operated patients 6-48 months later (mean of 14 months) did not demonstrate any increase in tumour size so that a waiting attitude seems justified: benign tumours are clearly much more frequent than malignant ones. However, if the tumour diameter is greater than 6 cm, an adrenalectomy is indicated because of the danger of malignancy.

Adenoma↗
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↗
PubMed1989

Management and efficacy of intensified insulin therapy--starting in outpatients.

Diabetic patients under multiple injection insulin therapy (i.e., intensified insulin therapy, IIT) usually start this treatment during hospitalization. We report here on the logistics, efficacy, and safety of IIT, started in outpatients. Over 8 months, 52 type I and type II diabetics were followed up whose insulin regimens consecutively had been changed from conventional therapy to IIT. Two different IIT strategies were compared: free mixtures of regular and intermediate (12 hrs)-acting insulin versus the basal and prandial insulin treatment with preprandial injections of regular insulin, and ultralente (24 hrs-acting) or intermediate insulin for the basal demand. After 8 months HbA1 levels had decreased from 10.6% +/- 2.4% to 8.0% +/- 1.3% (mean +/- SD). There was no difference between the two regimens with respect to metabolic control; but type II patients maintained the lowered HbA1 levels better than type I patients. Only two patients were hospitalized during the follow-up time because of severe hypoglycemia. An increase of body weight due to the diet liberalization during IIT became a problem in one-third of the patients. Our results suggest that outpatient initiation of IIT is safe and efficacious with respect to near-normoglycemic control. Weight control may become a problem in IIT patients.

Blood Glucose↗
PubMed1988

The effect of sodium valproate in Cushing's disease, Nelson's syndrome and Addison's disease.

UNLABELLED: We investigated the effect of sodium valproate on plasma ACTH and serum cortisol concentrations in different pathological states of ACTH hypersecretion. Five patients with pituitary dependent Cushing's syndrome, two patients with Nelson's syndrome and five patients with Addison's disease were studied. Neither a single dose nor long term administration of sodium valproate resulted in a significant decrease of plasma ACTH levels in patients with Cushing's disease and Nelson's syndrome. Furthermore, the response of ACTH and cortisol to stimulation with lysine-vasopressin was unaffected during acute and chronic treatment. Patients with Addison's disease showed a slight attenuation of the ACTH response to lysine-vasopressin as compared to placebo but the difference was not statistically significant. IN CONCLUSION: sodium valproate does not appear to be effective in controlling ACTH hypersecretion in pituitary dependent Cushing's syndrome.

Addison Disease↗
PubMed1988

Nonhypnotic low-dose etomidate for rapid correction of hypercortisolaemia in Cushing's syndrome.

We determined the adrenostatic potential of low-dose nonhypnotic etomidate in six patients with Cushing's syndrome (ectopic Cushing's syndrome, n = 2; Cushing's disease, n = 3; bilateral adrenal adenoma, n = 1). Etomidate was given as a continuous infusion for 32 h in a dose of 2.5 mg/h (n = 5) or 0.3 mg/kg/h (n = 3), respectively. Saline was given during a control period. The responsiveness to exogenous ACTH was studied during placebo and 7 and 31 h after commencing etomidate by administration of 250 micrograms 1-24 ACTH i.v. Etomidate (2.5 mg/h) led to a consistent decrease in serum cortisol in all patients from a mean of 39.4 +/- 13.3 to 21.1 +/- 5.7 micrograms/dl after 7 h (P less than 0.05 compared with placebo). After 24 h cortisol was reduced further to a mean steady state concentration of 12.3 +/- 5.7 micrograms/dl (P less than 0.05). At the end of the infusion period the cortisol increase in response to ACTH was reduced but not abolished. In contrast, a dose of 0.3 mg/kg/h etomidate induced unresponsiveness of serum cortisol to exogenous ACTH within 7 h. However, sedation was observed in two out of three patients at this dose, while during etomidate in a dose of 2.5 mg/h no side effects were seen. We conclude that low-dose nonhypnotic etomidate reduces serum cortisol to within the normal range in patients with Cushing's syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗