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Biomedical subjects

L M Sandler

Publications and source records attributed to L M Sandler.

At least 19 recordsLinked to original sources
PubMed1990

An evaluation of the distinction of ectopic and pituitary ACTH dependent Cushing's syndrome by clinical features, biochemical tests and radiological findings.

The efficiency of various laboratory and radiological investigations in the differentiation of ectopic from pituitary dependent Cushing's syndrome was studied, based on findings in 23 patients with verified Cushing's disease and seven patients with the ectopic ACTH syndrome. Clinical features strongly favouring the ectopic type were male sex and history for less than 18 months. Basal biochemical features strongly indicating the ectopic syndrome included plasma K+ less than 3.0 mmol/l and HCO3 greater than 30 mmol/l; serum cortisol at 9 a.m. or midnight of greater than 800 nmol/l; urine free cortisol greater than 1300 nmol/24 hours; plasma ACTH greater than 100 ng/l. In the high-dose dexamethasone suppression test, suppression by less than 50 per cent of 9 a.m. serum cortisol, urine free cortisol or 17-oxogenic steroids was usually indicative of an ectopic source of ACTH. A mean suppressed value of greater than 450 nmol/l for the 9 a.m. and midnight cortisol combined occurred in all of those with the ectopic syndrome, but in none of the 23 patients with Cushing's disease. For urine free cortisol, a mean suppressed value of less than 1000 nmol/24 hours was found in all patients with Cushing's disease, but in none of those in the ectopic group. In the metyrapone test, there was an increase of less than or equal to 3-fold in 11-deoxycortisol at 24 hours in patients with ectopic ACTH; the increase was greater than 3-fold in all but one of the patients with Cushing's disease. Failure to respond to either dexamethasone or metyrapone was found in only one of the patients with Cushing's disease (Patient 16); in the ectopic group, all patients except Patient D failed to respond to either test. It is concluded that patients presenting with clinically obvious Cushing's syndrome along with measurable plasma ACTH can be reliably divided by conventional tests into those that are driven from the pituitary and those driven by ectopic ACTH.

ACTH Syndrome, Ectopic↗
PubMed1990

Pharmacokinetics of the long-acting somatostatin analogue octreotide (SMS 201-995) in acromegaly.

A single-dose study was performed to examine the pharmacokinetics of subcutaneous octreotide in acromegalic patients and to investigate the relationship between growth hormone and the elimination half-life of the drug. Fourteen acromegalic patients (six men and eight women; age range 35-59 years) who had previously received conventional treatment were studied. Two subjects were on long-term octreotide which had been discontinued 72 h before the study. Octreotide 100 micrograms was administered subcutaneously and plasma samples taken every 10 min for 1 h and then hourly for up to 8 h. Growth hormone was measured at 0, 2 and 8 h. Octreotide was rapidly absorbed with a mean (+/- SEM) t1/2abs of 5.4 min (+/- 0.8) peaking at a mean plasma concentration of 3.4 nmol/l (+/- 0.2) in 27.4 min (+/- 3.7). The monoexponential elimination phase had a mean half-life of 110 min (+/- 9.6). The apparent volume of distribution was 29.4 1 (+/- 1.9) and total clearance was 172 ml/min (+/- 10.4). These results were similar to those obtained in normal volunteers. There was no simple relationship between the level of growth hormone and the half-life of octreotide. Growth hormone levels ranged from 2.5 to 34.0 mIU/l but were only greater than 10 mIU/l in three subjects. Further studies of octreotide pharmacokinetics are needed in untreated patients with acromegaly with raised growth hormone levels.

Acromegaly↗
PubMed1987

Effective long-term treatment of acromegaly with a long-acting somatostatin analogue (SMS 201-995).

Nine acromegalic patients, six previously untreated, were studied before and after 3-15 months of treatment with a long-acting somatostatin analogue (SMS 201-995; 100 micrograms injected s.c. three times daily). During treatment, the mean (+/- SEM) 24-h GH concentration fell from 82 +/- 22 mIU/l to 33 +/- 7 mIU/l (P less than 0.001), and eight of the 9 patients showed a reduction of at least 50% in GH levels in the fasting state and/or during a glucose tolerance test. There was a significant 30% fall in serum concentrations of insulin-like growth factor (IGF-1) with SMS. All patients showed rapid clinical improvement, with diminished sweating and headaches, and reduction in skinfold thickness, hand volumes and finger size. Computer tomographic scanning of the pituitary in eight patients showed no change in the size of the pituitary tumour during treatment. The only side-effects of SMS noted were transient abdominal discomfort and loose stools in two patients on initiating therapy. Although fasting plasma glucose concentration did not change during treatment (5.4 +/- 0.3 vs 5.5 +/- 0.3 mmol/l), mean 24-h plasma glucose concentration was higher with SMS (6.6 +/- 0.5 mmol/l vs 6.0 +/- 0.4 mmol/l; P less than 0.02). Mean 24-h plasma insulin concentration fell from 87 +/- 11 mIU/l before treatment to 39 +/- 6 mIU/l during treatment (P less than 0.005). No change in other anterior pituitary hormones was observed. SMS appears to be a safe, rapidly effective, long-term treatment for certain patients with acromegaly.

Acromegaly↗
PubMed1987

Long term follow-up of patients with Cushing's disease treated by interstitial irradiation.

The first 86 patients with Cushing's disease treated with interstitial irradiation (by needle implantation) as the sole therapy were reviewed. In the 82 patients who were reassessed 1 yr after treatment 63 (77%) achieved remission. This study comprises the outcome and complications in the 54 patients who had a remission and whom we were able to follow. The follow-up period ranged from 3-26 yr (mean, 10.5) from the time of remission. No instance of clinical or radiological relapse has occurred. Of these 54 patients, yttrium-90 alone was used in 32, of whom 12 (37%) required corticosteroid or T4 replacement therapy in a mean time of 3.5 months; in 7 of these 12 we elected to give an ablative dose. Gold-198 alone was used in 15 patients, of whom 7 (47%) developed hypopituitarism in a mean time of 76 months. Both isotopes were used in 7 patients. A diurnal serum cortisol rhythm was found in 28 of the 31 patients who were not receiving corticosteroid therapy. In 5 of the 7 patients with an initially abnormal pituitary fossa, serial radiological studies revealed remodelling in 3. There have been no complications in the last 17 years. Pituitary implantation with yttrium-90 is an effective alternative to transsphenoidal hypophysectomy, with a high remission rate, no recurrence (as yet), no operative complications, and avoidance of hormone replacement in the majority.

Adolescent↗
PubMed1986

Combined use of vasopressin and synthetic hypothalamic releasing factors as a new test of anterior pituitary function.

Nine normal volunteers and 15 patients with pituitary disorders were given a combined test of anterior pituitary function using four hypothalamic releasing factors and arginine vasopressin. Rapid sequential intravenous infusions of human corticotrophin releasing factor 100 micrograms, growth hormone releasing factor 100 micrograms, luteinising hormone releasing hormone 100 micrograms, and thyrotrophin releasing hormone 200 micrograms were administered. Arginine vasopressin (10 pressor units) was given intramuscularly at the same time. Plasma or serum samples were assayed for concentrations of cortisol, growth hormone, luteinising hormone, follicle stimulating hormone, prolactin, and thyroid stimulating hormone at multiple times for 120 minutes. No troublesome side effects occurred. The results of the releasing factor combined test with arginine vasopressin were compared in the same subjects with a conventional combined test using insulin together with thyrotrophin releasing hormone and luteinising hormone releasing hormone. No difference was observed in the basal and peak concentrations of luteinising hormone, follicle stimulating hormone, thyroid stimulating hormone, and prolactin. Both cortisol and growth hormone responses to the releasing factors with arginine vasopressin were much greater than those seen with insulin induced hypoglycaemia or the combined releasing factors without arginine vasopressin. Patients with pituitary hypo-function were similarly recognised in both studies. There was a rapid increase in all hormone values with a peak usually by 60 minutes. In most people adequate assessment of individual hormone reserves may be achieved using basal, 30 minute, and 60 minute samples. This new combined releasing factor test appears to be a safe, rapid, and useful test of anterior pituitary function.

Adult↗
PubMed1984

Computed tomography of sellar and parasellar lesions.

The findings in 50 patients examined by computed tomography (CT) of the pituitary fossa are described. The appearances in 43 were judged to be abnormal, four were normal and three were 'doubtful'. Abnormal features included deviation of the pituitary stalk (seven), localised increased enhancement after intravenous injection of contrast medium (18) and extrasellar extension of tumour (11). The CT scans enabled diagnoses of pituitary microadenoma, empty sella and combinations of the two to be made. Modern CT scanners (third or fourth generation) provide detailed information enabling the optimum assessment and treatment of sellar and parasellar lesions.

Adolescent↗
PubMed1984

Studies of the hypercalcaemia of sarcoidosis: effect of steroids and exogenous vitamin D3 on the circulating concentrations of 1,25-dihydroxy vitamin D3.

Hypercalcaemia in six patients with sarcoidosis was associated with elevated circulating 1,25-dihydroxy vitamin D3 (187-475 pmol/l): the concentration of this metabolite of vitamin D was a function of the concentration of its precursor, 25-hydroxy vitamin D which remained within the normal range. Corticosteroids, in reducing serum calcium, eliminated this abnormal substrate--product relationship by rapidly reducing circulating 1,25-dihydroxy vitamin D3 while having no effect on 25-hydroxy vitamin D. The fall in circulating 1,25-dihydroxy vitamin D3 preceded the fall of calcium. Studies on the clearance of exogenous 1,25-dihydroxy vitamin D3 indicated that during hypercalcaemic episodes, the plasma disappearance time of the sterol was delayed and that this reverted to normal with steroid therapy. Administration of vitamin D3 to these patients with sarcoidosis increased the circulating concentration of 1,25-dihydroxy vitamin D3 and this resulted in hypercalcaemia, thus accounting for their hypersensitivity to vitamin D and sunlight.

Adult↗
PubMed1983

Familial benign hypercalcaemia. Study of a large family.

Twenty-seven hypercalcaemic subjects were identified in three generations of a family. There were no clinical complications of chronic hypercalcaemia, but five had had parathyroid surgery which was unsuccessful in four. Twenty of the twenty-seven subjects were compared with twenty-four normocalcaemic controls from the same family and the findings were also compared with those from forty patients with surgically proven primary hyperparathyroidism. The relation between the serum and urinary calcium levels was studied by means of an oral calcium loading test. The ratio of calcium clearance to creatinine clearance was normal in this family (but elevated in the patients with primary hyperparathyroidism) and the concentration of parathyroid hormone was normal, as was the total urinary excretion of cyclic AMP. Thus, there was no evidence of either suppressed or increased parathyroid activity in this familial condition. Basal urinary calcium excretion was normal under steady-state conditions indicating that the hypercalcaemia could not be attributed to either increased bone resorption or increased calcium absorption from the gut. In accordance with this, the serum levels of 1,25-dihydroxycholecalciferol were normal. The hypercalcaemia in this condition can be accounted for in full by an increase in renal tubular reabsorption of calcium, and thus differs from that of primary hyperparathyroidism in which there is increased production of calcium from gut and/or bone as well as an increase in renal tubular reabsorption of calcium. Although the serum phosphate and renal tubular reabsorption of phosphate were both low in patients with familial benign hypercalcaemia, they were not as low as in patients with the same degree of hypercalcaemia due to primary hyperparathyroidism. The changes in phosphate transport in familial benign hypercalcaemia could be explained as a secondary effect of the increased filtered load of calcium in the kidney. The tendency towards hypermagnesaemia in our patients, which contrasts with a tendency towards hypomagnesaemia in primary hyperparathyroidism, could also be explained as a secondary effect of the abnormality of renal tubular reabsorption of calcium. Increased renal tubular calcium reabsorption and persistent normal functioning of the parathyroid glands in the face of hypercalcaemia remain the sole definite abnormalities of the syndrome.

Adolescent↗
PubMed1982

The effect of renal function on changes in circulating concentrations of 1,25-dihydroxycholecalciferol after an oral dose.

1. 1,25- Dihydroxycholecalciferol [1,25-(OH)2D3] was administered orally to four normal subjects and six patients with chronic renal failure not on dialysis. The serum concentration of 1,25-(OH)2D3 was measured by radioimmunoassay in both groups from samples taken before, and at regular intervals up to 48 h after, the oral dose. 2. The plasma half-time for the disappearance of the administered 1,25-(OH)2D3 was estimated by determining the time for a 50% reduction from the peak increment of the sterol. In normal subjects the calculated value ranged from 5 to 8 h compared with 18 to 44 h in uraemic patients. 3. It appears from our studies that in uraemic subjects there is impaired ability to metabolize or excrete 1,25-(OH)2D3.

Adult↗
PubMed1982

Demonstration of circulating 1,24,25-trihydroxyvitamin D3 in man by radioimmunoassay.

1,24,25-trihydroxyvitamin D3 has been detected in human serum using a sensitive radioimmunoassay. Tritiated 1,24,25-trihydroxyvitamin D3 was synthesized biologically and used as tracer to monitor the recovery of endogenous metabolite during isolation from serum. Circulating 1,24,25(OH)3D3 in normal subjects ranged from 9.3 to 18.5 pmol/l but was not detectable (less than 2.3 pmol/l) in serum from nephrectomized subjects. The trihydroxymetabolite was elevated in three out of four vitamin D deficient subjects who were being treated with vitamin D3.

Cholecalciferol↗
PubMed1982

Long-term effects of 1,25-dihydroxy vitamin D3 and 24,25-dihydroxy vitamin D3 in renal osteodystrophy.

Twenty-three patients with end-stage renal failure on maintenance haemodialysis were treated with 1,25-dihydroxy vitamin D3 or 24-25-dihydroxy vitamin D3 for 3-32 months (total 232 patient months). Treatment with 1,25-dihydroxy vitamin D3 was marked by symptomatic, biochemical and histological improvements in the majority of patients. In contrast, treatment with 24,25-dihydroxy vitamin D3 produced no biochemical or histological improvements and such patients developed severe symptomatic bone disease. Successful renal transplantation resulted in rapid improvement in symptoms, biochemistry and bone histology in nine of 10 patients irrespective of whether prior treatment was with 1,25-dihydroxy vitamin D3, 24,25-dihydroxy vitamin D3 or both. During treatment with 1,25-dihydroxy vitamin D3 progressive reduction in dosage was required in the majority of patients because of hypercalcaemia, which was rapidly corrected by stopping treatment for a few days. Hypercalcaemia did not occur until serum alkaline phosphatase (AP) and amino terminal parathyroid hormone (N-PTH) had fallen towards normal. Treatment failure was uncommon in 1,25-dihydroxy vitamin D3-treated patients and was characterized by the early development of hypercalcaemia. Addition of 24,25-dihydroxy vitamin D3 in such patients rendered the hypercalcaemia more manageable but did not lead to any further improvement in biochemistry or bone histology. Treatment with 24,25-dihydroxy vitamin D3 was accompanied by the development of severe symptomatic bone disease in the majority of patients and a characteristic pattern of biochemical abnormalities with hypocalcaemia and rises in AP and N-PTH. Substitution of 1,25-dihydroxy vitamin D3 treatment for 24,25-dihydroxy vitamin D3 in these patients resulted in prompt improvement in clinical, biochemical and histological abnormalities. Successful renal transplantation was accompanied by rapid resolution of clinical, biochemical and histological features of renal osteodystrophy irrespective of whether previous treatment was with 1,25-dihydroxy vitamin D3 or 24,25-dihydroxy vitamin D3. Hypophosphataemia was common in the early months after renal transplantation without evidence of continuing hyperparathyroidism. The studies have confirmed that 1,25-dihydroxy vitamin D3 is effective in controlling clinical, biochemical and histological features of renal osteodystrophy while 24,25-dihydroxy vitamin D3 did not have a useful therapeutic effect in the dose used.

24,25-Dihydroxyvitamin D 3↗
PubMed1980

Familial hyperparathyroidism.

A mother and her 12-year-old son both had a parathyroid adenoma. They represent a further example of dominant inheritance of isolated hyperparathyroidism.

Adenoma↗