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Biomedical subjects

H A Kellett

Publications and source records attributed to H A Kellett.

17 recordsLinked to original sources
PubMed1988

Hyperandrogenism, insulin resistance, acanthosis nigricans, and systemic lupus erythematosis associated with insulin receptor antibodies.

We report a young woman with systemic lupus erythematosis (SLE) who developed diabetes secondary to extreme insulin resistance, associated with severe hyperandrogenism and acanthosis nigricans. Her insulin resistance was found to be associated with high titers of insulin receptor antibodies. The hyperandrogenism has been favourably influenced by cyclical treatment with cyproterone acetate and ethinyl oestradiol, but the insulin resistance and acanthosis nigricans have remained unmodified after 15 months of follow up.

Acanthosis Nigricans↗
PubMed1986

Problems of anticoagulation with warfarin in hyperthyroidism.

From clinical observation it would appear that hyperthyroid patients are particularly sensitive to the anticoagulant effects of warfarin. A study was made of clotting factors prothrombin (II), VII, procoagulant VIII (VIIIC), IX and X and of prothrombin ratio (PTR) and partial thromboplastin time with kaolin (PTT-K). These parameters and warfarin levels were measured before and following a single dose of warfarin given to five patients when hyperthyroid and again when euthyroid. Hyperthyroidism was associated with lower activity of factor II and a shorter PTT-K. Warfarin produced a greater fall in factors II and VII and a greater increase in PTR and PTT-K in the hyperthyroid state than in the euthyroid state. The enhanced response to warfarin in hyperthyroidism was, however, relatively greater for the PTR than for the PTT-K. In order to produce adequate protection against intravascular thrombosis by a suitable prolongation of the PTT-K, it may be necessary in hyperthyroid patients to extend the PTR beyond the normal therapeutic range.

Aged↗
PubMed1985

Limitations of new thyroid function tests in pregnancy.

Sensitive immunoradiometric assays (IRMA) for TSH and radioimmunoassay (RIA) kits for free thyroid hormones (fT4, fT3) are becoming increasingly used for routine thyroid investigations. We have assessed these tests in 93 euthyroid pregnant women. Mean fT4 and fT3 values decreased with gestation by 24-27% and 14-35%, respectively, using several analogue RIA kits. Some patients had free hormone values which fell below the reference range derived from non-pregnant euthyroid patients. By contrast, the fT4 concentrations measured by direct equilibrium dialysis fell by only 16% with all values within the reference range. Serum non-esterified fatty acid (NEFA) levels (non-fasting) did not correlate with fT4 and fT3 but a spurious effect of serum albumin levels on the free hormone kits was suggested. TSH results showed that the majority of subjects had lower values measured by IRMA than by RIA. Three patients had basal TSH (IRMA) below the mean detection limit of the assay; this could have been falsely interpreted as indicating hyperthyroidism. We conclude that, as with longer established thyroid function tests, special care must be taken in interpreting results of these new thyroid function tests in pregnancy.

Fatty Acids, Nonesterified↗
PubMed1985

Raised plasma glutathione S-transferase values in hyperthyroidism and in hypothyroid patients receiving thyroxine replacement: evidence for hepatic damage.

Using plasma glutathione S-transferase measurements hepatocellular integrity was assessed in groups of hyperthyroid and hypothyroid patients before and after treatment. Ten of 14 hyperthyroid patients had clearly raised plasma glutathione S-transferase values at presentation and in each patient treatment with either iodine-131 or carbimazole resulted in a significant fall in glutathione S-transferase. The eight hypothyroid patients had normal glutathione S-transferase values at presentation and all showed a significant increase in these after thyroxine replacement therapy. In three of these patients in whom standard doses of replacement therapy were associated with a raised free thyroxine (T4) concentration but normal total and free triiodothyronine (T3) values glutathione S-transferase was increased. Similar though less consistent changes were seen in the results of standard chemical tests of liver function. It is concluded that hyperthyroidism may produce subclinical liver damage in a high proportion of patients and that this resolves with effective treatment. More important, the data suggest that hypothyroid patients receiving thyroxine replacement therapy may have similar subclinical liver damage. Patients receiving thyroxine should be monitored by the measurement of free, not total hormone concentrations, and in those in whom free T4 is raised the dose of thyroxine should be reduced. It would also be expedient to include periodic biochemical assessment of liver function in patients receiving thyroxine.

Adult↗
PubMed1985

A new strategy for thyroid function testing.

In view of the increasing number of in-vitro tests of thyroid function, rationalization of the biochemical assessment of patients with suspected thyroid disease was attempted. In addition to clinical examination of 285 consecutive new referrals to a thyroid clinic, measurements were made of serum total and free triiodothyronine (T3) and thyroxine (T4) and of thyrotropin (TSH) by radioimmunoassay before and 20 min after thyrotropin-releasing hormone (TRH) and basal TSH by immunoradiometric assay (IRMA). Analysis of these results demonstrated that: (i) a detectable and normal TSH (IRMA) result indicates that the patient is euthyroid and obviates the need for measurement of thyroid hormones and (ii) a raised or undetectable TSH (IRMA) level should be followed by measurement of free T4 (and rarely also free T3) to distinguish between subclinical and overt hypothyroidism and hyperthyroidism. This policy would considerably reduce the number of in-vitro thyroid function tests without resulting in either a delay in diagnosis or a reduction in its accuracy.

Adolescent↗
PubMed1985

Accuracy and precision of five analog radioimmunoassays for free thyroxin compared.

We compared the precision of free thyroxin (FT4) measurements by kits involving analog RIA and the use of antibody-coated tubes (Becton Dickinson and Coat-A-Count), magnetic separation (Amerlex Magnetic and Corning Magic), or centrifugation of antibodies linked to solid beads (Amerlex). Results of kits with magnetic separation were the most reproducible. Amerlex, Amerlex Magnetic, and Becton Dickinson kits gave values comparing best with those obtained by direct equilibrium dialysis. Coat-A-Count and Corning Magic results differed significantly from dialysis values, both for patients' samples and kit standards. The kits had equal diagnostic efficiency in patients with suspected thyroid disease. On measurement of FT4 some patients were reclassified from "subclinical thyroid disease" to "overt disease." Most patients with triiodothyronine thyrotoxicosis had increased FT4. Several kit values were low for pregnant women and patients with nonthyroidal illness but the Amerlex and Amerlex Magnetic assays had fewer low results. The Amerlex Magnetic FT4 assay gave the best precision, agreement with the reference method, and diagnostic efficiency.

Dialysis↗
PubMed1984

A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.

Adult↗
PubMed1984

A monoclonal antibody-based immunoradiometric assay for h-LH.

An immunoradiometric assay (IRMA) for h-LH based upon an 125I-labelled mouse monoclonal antibody (MAb) to h-LH with an effective equilibrium constant of 5.8 X 10(9) l/mol is described. A total incubation time of 3 h at room temperature was required, separation by means of the sucrose layering procedure took a further 1 h and counting times were 1 min/tube. Using the first IRP for h-LH (prep. 68/40) as standard, the detection limit was 0.1 U/l serum and the within-assay CV for duplicate determinations was less than 10% over the range 1-280 U/l and less than 3% at 10-100 U/l. The epitope, with which the MAb reacted, shared structures, on the alpha- and beta-subunits of LH since the assay responded to the intact hormone, but not to either of the subunits. Specificity was greater than 100 000:1 for h-LH vs. h-FSH and greater than 10 000:1 for h-LH vs. h-TSH. h-CG and h-LH were approximately equipotent. The results on 604 unselected samples were generally very similar to those found by RIA except at levels below 2 U/l for which the IRMA regularly gave lower results suggesting relative freedom from non-specific serum effects. The new assay, based upon potentially limitless supplies of a very stable reagent offers advantages of speed, sensitivity, range, and precision over conventional RIA. The specificity appears to be excellent. Although there are marginally more steps the total staff involvement is less than with conventional methods employing centrifugation.

Animals↗
PubMed1983

Hyperthyroidism due to a thyrotrophin-secreting microadenoma.

We report a 63-year-old female with a TSH-secreting pituitary adenoma causing hyperthyroidism. This case is apparently unique, and challenges the present concept of dividing patients with inappropriate TSH secretion into tumour and non-tumour groups on the basis of conventional pituitary fossa radiology.

Adenoma↗
PubMed1982

Does calcitonin cause hypocalcaemia after thyroidectomy?

Plasma calcitonin, parathyroid hormone, total thyroid hormones and calcium were measured in 6 patients before, during and after thyroidectomy for hyperthyroidism. In 4 patients, plasma calcium fell postoperatively by 0.23--0.46 mmol/l, but there was no change in calcitonin or parathyroid hormone levels. In one patient, in whom there was a postoperative fall in plasma calcium of 0.55 mmol/l, thyroid hormones rose to a peak at 1 h and calcitonin to a peak at 12 h after resection. However, the rise in calcitonin occurred 8 h after the initial decrease in plasma calcium. In this patient, parathyroid hormone levels showed a slight rise only. It is concluded that, while thyroid hormones and calcitonin may leak from the damaged thyroid remnant after surgery, it is unlikely that calcitonin is important in the production of postoperative hypocalcaemia. However, impaired parathyroid hormone secretion may be a contributing factor.

Adolescent↗
PubMed1982

What is the significance of raised plasma TSH levels after thyroid surgery?

Thyroid function was assessed prospectively for five years in 73 patients treated surgically for Graves's disease. No patient developed hypothyroidism after the sixth postoperative month, despite the presence of raised plasma TSH levels in 70 per cent of euthyroid patients at the end of the first year. Indeed, in those with evidence of temporary hypothyroidism (low T4, raised TSh at 3 months but normalisation of T4 at 6 months) plasma TSH continued to fall for up to three years. The majority (6) of patients developing recurrent hyperthyroidism did so within the first year, but in one of three patients who relapsed subsequently, plasma TSH had been elevated at one year. Plasma TSH cannot be used to predict thyroid status following surgery for Graves' disease. Although regular review remains necessary, it should not include measurement of TSH unless this is needed to confirm the validity of a low thyroxine level after the third postoperative month and before starting permanent replacement therapy.

Adult↗
PubMed1982

Prolactin response to metoclopramide in hyperthyroidism.

The response of PRL to the oral administration of the dopamine receptor-blocking agent metoclopramide and the effect of metoclopramide on the TRH-induced release of PRL and TSH were measured in eight patients with hyperthyroidism and in eight age- and sex-matched euthyroid controls. As expected from the known direct inhibitory influence of thyroid hormones on pituitary TSH secretion, there was no TSH rise in response to metoclopramide in either group. PRL levels, on the other hand, rose significantly after the administration of metoclopramide in both the hyperthyroid and euthyroid subjects (P less than 0.0005 at 60 and 120 min). However, the increase in PRL at 120 min was significantly less in the hyperthyroid subjects than in the euthyroid controls (P less than 0.0025). Furthermore, the administration of metoclopramide failed to reestablish normal responsiveness of either PRL or TSH to TRH in the hyperthyroid subjects. We have previously suggested that thyroid hormones inhibit PRL secretion by stimulating the hypothalamic secretion of dopamine. These results suggest, however, that elevated levels of thyroid hormones also inhibit PRL release directly at the anterior pituitary level.

Administration, Oral↗
PubMedDate not supplied

Bacteriuria and autonomic nerve function in diabetic women.

Significant bacteriuria (viable count greater than or equal to 10(5)/ml) was found on single testing in 10% of 400 consecutive diabetic women aged 15-65 yr routinely attending a diabetic clinic. Twenty patients with and 21 without significant bacteriuria were then randomly selected for measurement of cardiovascular autonomic reflexes, bladder ultrasound, and mictiography. There were no significant differences between these two groups in age, duration and type of diabetes, glycosylated hemoglobin, blood urea, and creatinine. Abnormalities of cardiovascular autonomic function were more common in the bacteriuric group (P less than .01). Although the bacteriuric group voided a smaller volume of urine, none had evidence of increased residual bladder volume of urine on ultrasound. Diabetic women with cardiovascular autonomic neuropathy appear to be at increased risk of developing bacteriuria. However, age is probably the most important factor influencing the prevalence of bacteriuria in diabetic and in nondiabetic women.

Adolescent↗