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.

The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test.

BACKGROUND: In suspected hypercortisolism, the 1 mg dexamethasone suppression test is the usual initial test. In fertile women, false-positive test results are often due to the use of oral contraceptives. By elevating cortisol-binding globulin these contraceptives increase the total serum cortisol concentration. The aim of this study was to assess the duration and degree of influence of oral contraceptives on the low-dose dexamethasone suppression test. METHODS: Thirteen healthy female volunteers without symptoms or signs of overt hypercortisolism, aged 18-55 years, who were using oral contraceptives, underwent a 1 mg dexamethasone suppression test. Tests were repeated one and six weeks after withdrawal of the contraceptive. In addition, 24-hour urinary cortisol excretion and late-night salivary cortisol were measured. RESULTS: Of the 13 volunteers (62%) eight had inadequate suppression of cortisol by 1 mg dexamethasone while using oral contraceptives. One week after the contraceptive was withdrawn, the number of false-positive results significantly decreased to 1 (8%, p < 0.02). Six weeks after discontinuation, all tests were normal. None of the 24-hour urinary cortisol samples and just one late-night salivary cortisol level was elevated. CONCLUSION: The results of the 1 mg dexamethasone suppression test performed one week after cessation of oral contraceptives are accurate in almost all subjects. In case of inadequate suppression, a second test may be performed after six weeks. In this manner the 1 mg dexamethasone suppression test can reliably be done at the end of a seven-day break from contraceptive use in nearly all cases.

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.

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.

Oscillating thyroid function ("reculer pour mieux sauter").

Evolution from hypo- to hyperthyroidism is a rare phenomenon. The clinical course is described of 2 patients with transient hypothyroidism proceeding to hyperthyroidism.

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.

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.

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.

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.

[Hypercalcemia caused by lithium medication in a female patient with a bipolar affective disorder]. / Hypercalciëmie door lithiummedicatie bij een patiënte met een bipolaire affectieve stoornis.

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.

[A patient with a palpable nodule in the throat due to a cystic parathyroid adenoma]. / Een patiënte met een palpabele zwelling in de hals door een cysteus bijschildklieradenoom.

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.

MIDD or MELAS : that's not the question MIDD evolving into MELAS : a severe phenotype of the m.3243A>G mutation due to paternal co-inheritance of type 2 diabetes and a high heteroplasmy level.

Maternally inherited diabetes and deafness (MIDD) and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) are different syndromes, but are caused by the same m.3243A>G mutation in mitochondrial DNA. Why some patients develop MIDD while others MELAS is unknown, but may be related to heteroplasmy level. Progression from MIDD to MELAS has not been described. Here we report a patient with MIDD who over time developed severe insulin resistance and symptoms and signs consistent with MELAS. The most likely explanation here was paternal co-inheritance of type 2 diabetes in combination with a high heteroplasmy level. The present case showing evolution of MIDD to MELAS supports the concept that both syndromes can be regarded as two phenotypes of the same disease.