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Biomedical subjects

A H Mudde

Publications and source records attributed to A H Mudde.

At least 19 recordsLinked to original sources

Fibrillary glomerulonephritis in a patient with type 2 diabetes mellitus.

We report a 62-year-old man with documented type 2 diabetes mellitus and hypertension, who presented with a rapid deterioration in renal function. The sudden decrease in renal function in this well-controlled diabetic patient prompted us to consider a nondiabetic and nonhypertensive cause. The urinary sediment showed a glomerular haematuria suggestive of glomerulonephritis. A diagnosis of fibrillary glomerulonephritis was made on renal biopsy. Fibrillary glomerulonephritis is a rarely diagnosed disease with clinical manifestations such as proteinuria, microscopic haematuria, nephrotic syndrome and impairment of renal function. A diagnosis of fibrillary glomerulonephritis can only be made by electronmicroscopy of the renal tissue. In this case report the spectrum of this disease is reviewed.

Biopsy↗

[A patient with a palpable nodule in the throat due to a cystic parathyroid adenoma].

In a 38-year-old woman who was examined because of an otherwise asymptomatic palpable nodule in the thyroid region, a cystic parathyroid adenoma was diagnosed. The aspirate was clear with a slight yellowish colour and a very high parathormone concentration. The serum-calcium concentration was also very high. The lesion was surgically removed. The surgical specimen contained a parathyroid adenoma with pseudocystic degenerative changes. The patient recovered fully.

Adenoma↗

Glucose and cardiovascular risk.

The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages between normal glucose homeostasis and diabetes, based on fasting and challenged glucose levels, respectively. Criteria were established for 'the metabolic syndrome', as a cluster of cardiovascular risk factors that frequently coincides with the abnormal glucose tolerance state. The extent to which the glucose level itself should be regarded as a cardiovascular risk factor is the subject of ongoing debate. Recent research suggests that cardiovascular risk is related to the plasma glucose level even in the normal range of glucose concentrations. The impact of glucose in relation to cardiovascular events is discussed in this review.

Blood Glucose↗

Severe hyponatraemia in an amiloride/hydrochlorothiazide-treated patient.

A 85-year-old woman treated with, among other drugs, a thiazide diuretic presented with a severe hyponatraemia. She met several of the criteria for SIADH and, besides drugs, no cause for SIADH was found. After stopping the thiazide diuretic and restricting fluid intake the patient recovered fully. It was later proved that the thiazide was the cause of the water intoxication by rechallenging the patient with a single dose of amiloride/hydrochlorothiazide 5/50 mg. This "thiazide provocation test" showed its usefulness in the differential diagnosis of suspected SIADH. Moreover, the test demonstrated the paradoxal effect of thiazide diuretics to cause water retention in susceptible patients.

Aged↗

Preclinical Cushing's syndrome in patients with an adrenal incidentaloma.

BACKGROUND: Autonomous (hyper-)secretion of cortisol without classical stigmata of Cushing's syndrome occurs in 10-15% of patients with incidentally detected adrenal tumors (incidentalomas). METHODS: We present the clinical and biochemical data of four such patients. Two patients had hypertension and one both hypertension and non-insulin-dependent diabetes mellitus, but none showed classical stigmata of Cushing's syndrome. RESULTS: All patients showed insufficient suppression of plasma cortisol during a 1 mg dexamethasone screening test. Plasma ACTH levels were suppressed in all patients. However, in three out of four patients the diurnal rhythm of plasma cortisol was intact and these three patients also showed a response of plasma cortisol after administration of corticotropin-releasing hormone. All patients underwent unilateral adrenalectomy. A carcinoma was found in one patient and an adenoma in the remaining three. Postoperatively, blood pressure had normalized in 2 out of 3 hypertensive patients, whereas non-insulin-dependent diabetes mellitus had disappeared in 1 patient. Postoperative endocrine evaluation showed no abnormalities anymore. CONCLUSIONS: We conclude that dexamethasone testing may reveal autonomous (hyper-)secretion of cortisol in adrenal incidentalomas. Adrenalectomy should be considered, especially when hypertension and/or non-insulin-dependent diabetes mellitus are present. One should be alert to the development of adrenal insufficiency after unilateral adrenalectomy.

Adrenal Gland Neoplasms↗

Subclinical thyroid disease.

Thyroid disease can roughly be divided into functional and anatomical disorders. Subclinical disease is by definition not accompanied by symptoms or signs and usually goes unrecognized for the bearer (and the observer). In this communication an overview will be given of existing literature and some own results concerning subclinical hypothyroidism, subclinical thyrotoxicosis and thyroid incidentalomas. Apart from definitions, data on prevalence, clinical effects, prognostic significance and the need for and response to therapy will be discussed.

Humans↗

Metastatic follicular carcinoma of the thyroid: reappearance of radioiodine uptake.

Dedifferentiation of well-differentiated thyroid carcinoma is a well-known phenomenon that may lead to the disappearance of radioiodine uptake in tumors and the inability to treat patients with radioiodine. We report a patient in whom the 131I uptake progressively diminished to such low levels after a cumulative dose of 31.5 GBq that further 131I administration was considered nonbeneficial. Thereafter, metastases in the lungs and skeleton progressed. Because of the absence of any other therapeutic options, nearly 2 yr later we decided to reperform 131I measurements and scanning under hypothyroid conditions. All known metastatic lesions this time showed intense 131I uptake, more than 10-fold the previously measured values. High-dose 131I treatment was restarted.

Adenocarcinoma, Follicular↗

Bone metabolism during anti-thyroid drug treatment of endogenous subclinical hyperthyroidism.

OBJECTIVE: There is recent evidence that both exogenous and endogenous subclinical thyrotoxicoses are associated with decreased bone mineral density. Scanty information is available on bone metabolism in these conditions when euthyroidism is restored. We evaluated the effect of anti-thyroid drug treatment on bone metabolism in endogenous subclinical hyperthyroidism. DESIGN: Prospective follow-up study over 2 years during treatment with methimazole, with an untreated control group. SUBJECTS: Sixteen post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre, eight of whom were treated with methimazole. MEASUREMENTS: Serum concentrations of free T4, total T3, TSH, osteocalcin, urinary excretion of hydroxyproline and forearm bone mineral density were measured at regular intervals. RESULTS: Significant changes in serum osteocalcin concentration or urinary hydroxyproline excretion were not observed in either group. Distal, but not proximal, forearm bone mineral density, expressed as a percentage of the base-line value, was significantly (P < 0.05) higher in the treated than in the untreated subjects in the second year of treatment. CONCLUSION: Treatment with methimazole in post-menopausal women with endogenous subclinical hyperthyroidism associated with multinodular goitre can prevent excessive loss of bone, at least in the distal forearm.

Bone Density↗

[Hypercalcemia caused by lithium medication in a female patient with a bipolar affective disorder].

In a 68-year-old woman, who used lithium carbonate because of longstanding recurring depression, an association was found between hypercalcaemia and the use of lithium. The serum calcium concentration appeared to be significantly correlated with the serum lithium concentration (y = 2.38 + 0.37x; r = 0.36; p = 0.009). There was a significant inverse correlation between the ratio of 24-hour urinary calcium and creatinine excretion and the serum lithium concentration (y = 0.80 - 0.22x; r = 0.43; p = 0.030). The association of hypercalcaemia and use of lithium has been reported before. The finding may be due to an effect of lithium on the parthyroids and (or) on the kidneys.

Aged↗

Peripheral bone density in women with untreated multinodular goitre.

OBJECTIVES: We wished to determine whether women with multinodular goitre and spontaneous subclinical hyperthyroidism have decreased bone density. DESIGN AND SUBJECTS: Bone density was measured at the distal and proximal forearm. Data were expressed as Z-scores relative to the mean values out of 125 control subjects matched for age and menopause. The Z-scores of 23 women with subclinical hyperthyroid goitre (TSH < 0.1 mU/l and normal values for FT4 and total T3) and of 54 women with euthyroid goitre were compared. MEASUREMENTS: Bone density was measured by single photon absorptiometry. TSH was measured by IRMA, FT4 by RIA. RESULTS: Relative to the euthyroid goitre subjects the mean +/- SEM Z-scores of both the distal and proximal forearm density were lower (-0.69 +/- 0.17 vs -0.1 +/- 0.18, P < 0.05 and -0.5 +/- 0.18 vs 0.07 +/- 0.18, P < 0.05, respectively). Median (range) FT4 in the subclinical hyperthyroid goitre subjects was significantly higher than euthyroid goitre subjects (15.6 (11-23.2) pmol/l vs 11.9 (8.3-18.3) pmol/l, P < 0.001) although still within the normal range. FT4 correlated inversely with Z-scores of both distal and proximal forearm bone density in the subjects with subclinical hyperthyroidism (r = -0.42, P < 0.05 and r = -0.43, P < 0.05, respectively), but not in the euthyroid goitre subjects. CONCLUSION: These findings indicate that women with untreated multinodular goitre and subclinical hyperthyroidism have reduced bone density in the forearm.

Adult↗

Is there a relationship between thyroid function and serum osteocalcin in women with multinodular goitre? A preliminary report.

The relationship between thyroid function and serum osteocalcin was studied in a population of 27 women with multinodular goitre and normal serum concentrations of thyroid hormones. Seven patients were found to have suppressed TSH levels (less than 0.1 mU/l) as measured by an immunoradiometric assay. Osteocalcin was statistically significantly correlated with serum free thyroxine (FT4), both in the total population and in the subpopulation of patients with TSH greater than or equal to 0.1 mU/l (r = 0.61; P less than 0.001, resp. r = 0.51; P less than 0.05). Mean (+/- SEM) serum osteocalcin and FT4 were higher in the patients with suppressed TSH than in those with TSH greater than or equal to 0.1 mU/l (10.6 +/- 1.9 vs. 7.1 +/- 0.6 micrograms/l; P less than 0.05, resp. 16.3 +/- 1.4 vs. 13.3 +/- 0.5 pmol/l; P less than 0.02). This study suggests that women with multinodular goitre who proceed to autonomous function are at risk of developing osteoporosis even when thyroid hormone concentrations are in the normal range.

Adult↗

Facial dysmorphia, parathyroid and thymic dysfunction in the father of a newborn with the DiGeorge complex.

A boy born at full-term died after 14 days from cardiac failure. At autopsy DiGeorge complex was diagnosed. The father was found to have facial dysmorphia and hypocalcaemia. Investigations revealed no cause other than hypoparathyroidism associated with normal serum 1,25-dihydroxyvitamin D concentrations and normal renal handling of phosphate. Immunological tests, performed on two occasions with an interval of 9 months, revealed a decrease in the number of CD8+ lymphocytes, compatible with a partial thymus deficiency. The combination of facial dysmorphia with dysfunction of the thymus and the parathyroid glands can constitute a partial DiGeorge complex. The findings in this family are compared with reports of four other families with DiGeorge complex in two generations. In genetic counseling DiGeorge complex should be considered a heterogenous disorder. Screening of the parents for somatic stigmata, hypocalcaemia, disturbed cellular immunity, cardiac and chromosomal abnormalities is essential.

Adult↗

Ectopic production of 1,25-dihydroxyvitamin D by B-cell lymphoma as a cause of hypercalcemia.

A patient with long-standing rheumatoid arthritis developed hypercalcemia (3.13 mmol/l) and was subsequently found to have a B-cell lymphoma (centroblastic type). The hypercalcemia was associated with high circulating concentrations of 1,25-dihydroxyvitamin D (235 pmol/l) and both abnormalities were corrected with treatment. A lymph node was excised before treatment and was incubated in vitro with either labeled or unlabeled 25-hydroxyvitamin D3. After purification of the extract and chromatography on three different HPLC systems, material comigrating with authentic 1,25-dihydroxyvitamin D3 was identified. This was shown to bind to a specific chick intestinal cytosol receptor and to dilute in parallel with synthetic 1,25-dihydroxyvitamin D3 in the receptor binding assay. In conclusion, hypercalcemia in malignant B-cell lymphoma can be due to extrarenal production of 1,25-dihydroxyvitamin D by lymphomatous tissue.

Arthritis, Rheumatoid↗

Serum osteocalcin in Paget's disease of bone: basal concentrations and response to bisphosphonate treatment.

Serum osteocalcin concentrations were measured in 42 patients with Paget's disease of bone and elevated serum alkaline phosphatase (AP) levels. High serum osteocalcin levels were found in only 22 patients. Serum osteocalcin was significantly correlated with urinary hydroxyproline excretion (r = 0.747; P less than 0.001) and, to a lesser extent, with serum AP levels (r = 0.483; P less than 0.01). In 23 patients who were followed during treatment with iv (3-amino-1-hydroxypropylidene) 1,1-bisphosphonate (APD) for 10 days, a dissociation among these 3 biochemical parameters was found. Urinary hydroxyproline excretion fell significantly (P less than 0.001), serum AP levels decreased, but not significantly, and serum osteocalcin concentrations increased progressively (P less than 0.001). This increase was greater when initial levels were lower than expected for the activity of the disease. The rise in serum osteocalcin correlated significantly with the concomitant increase in serum 1,25-dihydroxyvitamin D concentrations. Three months after initiation of treatment, all 3 parameters, urinary OHP excretion, serum AP, and serum osteocalcin levels, were near or within the normal range. These results indicate that serum osteocalcin is not a clinically useful parameter for assessment of the activity of Paget's disease. Its basal concentrations lag behind those expected from the activity of the disease, suggesting defective osteocalcin production. It appears that the functions of osteocalcin and AP as well as their initial expression by the osteoblasts are different and that this difference may be important for the quality of bone formed in Paget's disease. APD can modulate the release of osteocalcin, possibly through stimulation of 1,25-dihydroxyvitamin D production, although other factors may be involved.

Adult↗