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Papers by John Galligan

Journal of Hepatology, 2010

Background & Aims: Adrenal insufficiency (AI) has been reported in patients with advanced liver d... more Background & Aims: Adrenal insufficiency (AI) has been reported in patients with advanced liver disease. Diagnosing AI is problematic owing to controversies in using total serum cortisol as a measure of adrenal function. No published data exist on directly measured plasma free cortisol (PFC) in patients with liver disease. Methods: This prospective study compared serum total and measured plasma free cortisol to evaluate adrenal function in clinically stable cirrhotic patients and healthy controls. Cortisol levels were measured at baseline and following 250 lg corticotrophin. AI was defined by total cortisol increments (delta cortisol) of less than 250 nmol/L, or a peak total cortisol under 500 nmol/L after cosyntropin. We used a peak plasma free cortisol concentration of 33 nmol/L as the threshold for AI. Results: Forty-three consecutive patients and 10 healthy controls were studied. Cirrhotic patients had significantly lower peak (526 vs. 649 nmol/L, p = 0.004) and delta total cortisol (264 vs. 397 nmol/L, p = 0.002) responses compared to healthy controls. However, basal plasma free cortisol was higher in patients (10.9 vs. 6.4 nmol/L, p = 0.03), and there were no differences in peak plasma free cortisol (p = 0.69) between the two groups. The prevalence of AI using total cortisol criteria was 58% compared to 12% using free cortisol (p <0.001). Conclusion: In patients with stable severe liver disease, a significant discrepancy exists between the rates of diagnosis of AI using the total and free cortisol criteria. We would advise caution in the interpretation of adrenal function testing using total cortisol measurements in this group.

Clinica Chimica Acta, 2011

Free cortisol (FC) can be calculated from measurements of total cortisol and binding proteins or ... more Free cortisol (FC) can be calculated from measurements of total cortisol and binding proteins or measured after mechanical separation of unbound and bound fractions by equilibrium dialysis or ultrafiltration. FC can then be measured indirectly by 3H-cortisol dilution or directly by immunologic or tandem mass spectrometry assays. We compared FC measured with ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC MS/MS) with 3H-cortisol dilution in ultrafiltrates and dialysates and also with calculated FC (Coolens equation). An adult FC reference interval was established. The UHPLC MS/MS and 3H-cortisol dilution methods were non-linearly related (Cusum linearity test p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) but well correlated (R2=0.984). FC calculated with Coolens equation agreed with the UHPLC MS/MS method. Impurity of 3H-cortisol and non-specific adsorption were excluded as causes on non-linearity. Ultrafiltration was linearly related to equilibrium dialysis, simpler to perform and more repeatable. A gender non-specific FC reference interval of 2.1-19.1 nmol/L was established. In view of the non-linearity between measuring techniques and the variability of reported reference ranges, care should be exercised in adopting a reference range. The ultrafiltration UHPLC MS/MS method we described is robust and suitable for use in a routine laboratory.

British Journal of Clinical Pharmacology, 1984

Plasma cortisol levels were measured before and for 6 h after the intravenous injection of 50 mg ... more Plasma cortisol levels were measured before and for 6 h after the intravenous injection of 50 mg cortisol as sodium succinate and oral administration of 50 mg cortisol and 50 mg cortisone acetate in 10 subjects with primary or secondary adrenal failure and in two normal volunteers. 2 Peak cortisol levels of 1518 + 190 nmol l-l (mean + s.e. mean) and 739 + 74 nmol 1-1 were found 1.46 + 0.25 and 1.79 + 0.16 h after oral cortisol and cortisone acetate respectively. The relative bioavailability of oral cortisol and cortisone acetate varied widely (cortisol 26-91%, mean 54 + 6.9%, cortisone acetate 21-95%, mean 44 + 6.5%) but despite this wide variation there was, in individual subjects, a highly significant correlation between the bioavailability of the two steroids (r = 0.870, P < 0.001). 3 This suggests that the wide interindividual variations in plasma cortisol levels seen after oral cortisone acetate are not related to variations in bioconversion of cortisone.

Clinical and Experimental Pharmacology and Physiology, 1991

World J Surgery, 1988

Ten patients with primary hyperparathyroidism caused by enlargement of a single parathyroid gland... more Ten patients with primary hyperparathyroidism caused by enlargement of a single parathyroid gland were studied preoperatively. An intravenous bolus of 4 g magnesium sulphate followed by a continuous infusion of 2 g per hour for 3 hours increased serum magnesium from 0.76 to 2.12 mmol/I (median values, p < 0.005). Serum C-terminal parathyroid hormone (PTH) decreased from 94 to 78 pmol/I (p < 0.005), and serum intact PTH from 7.0 to 4.8 pmol/l (p < 0.008). The PTH changes preceded decreases in serum total calcium from 2.79 to 2.55 mmol/I (p < 0.01), and serum ionized calcium from 1.52 to 1.45 mol/l (p < 0.007). Urinary calcium excretion increased and urinary phosphate excretion decreased. Serum phosphorus, pH, albumin, creatinine, alkaline phosphatase, and urinary cyclic AMP showed no significant changes. The study showed that an intravenous magnesium sulphate infusion which at least doubled the normal serum magnesium concentration significantly suppressed PTH secretion in patients with primary hyperparathyroidism and subsequently reduced the serum calcium concentration.

Australian and New Zealand journal of medicine, 1982

Serum thyroglobulin levels were measured by a sensitive radioimmunoassay in 76 patients whose dif... more Serum thyroglobulin levels were measured by a sensitive radioimmunoassay in 76 patients whose differentiated thyroid carcinoma had been treated by surgery with or without subsequent administration of radioactive iodine (131I). Examination of the results of 105 concomitant whole body 131I scan results and serum thyroglobulin levels showed a high degree (83.8%) of concordance between these two techniques. A significant correlation (r = 0.670, p less than 0.001) was found between serum thyroglobulin levels and quantitative 131I uptake in the neck and/or metastases in 42 patients in whom this was measured. Although a high degree of congruence was found between the results of 131I scans and the presence or absence of circulating thyroglobulin, 13 patients with negative scans using conventional doses of 131I had measurable levels of thyroglobulin. Eight of these patients had or subsequently developed evidence of residual thyroid tissue or metastatic carcinoma. The measurement of serum thy...

Australian and New Zealand journal of medicine, 1986

Fifty of 66 patients whose thyroid function had previously been assessed 7-139 months after irrad... more Fifty of 66 patients whose thyroid function had previously been assessed 7-139 months after irradiation for Hodgkin's disease were re-evaluated 35 +/- 3 months later. They could be divided into three groups: those whose thyroid function had been normal in the first study (N = 26), those who had had asymptomatic impaired thyroid reserve (N = 19), and those in whom evidence of Graves' disease had developed (N = 5). The 26 patients who had been euthyroid when first studied had developed significant increases in mean thyroid-stimulating hormone (TSH) levels (basal and following thyrotrophin releasing hormone) without changes in mean free thyroxine index (FTI). In three of these patients, each studied within six years of irradiation, basal TSH had risen to hypothyroid levels. There were no significant changes in mean FTI or basal and peak TSH in 19 patients who had demonstrated impaired thyroid reserve in the first study. The cumulative incidence of impaired thyroid reserve in th...

The Journal of Clinical Endocrinology & Metabolism, 2015

Context: Hypercalcemia is a common complication of cancer with parathyroid hormone related peptid... more Context: Hypercalcemia is a common complication of cancer with parathyroid hormone related peptide (PTHrP) an important mediator. Literature on the underlying causes of PTHrP-mediated hypercalcemia, in both malignant and benign conditions, is limited to small case series and case reports. Objective: To systematically identify a large series of cases of PTHrP-mediated hypercalcemia, to document differences in demographics and clinical course between malignant and benign etiologies. Design, Setting, Patients: Hospital-based, retrospective case series that identified subjects from 1999 to 2010 from the public hospital system in Queensland, Australia. Included subjects were 18 years and over and had persistent hypercalcemia with simultaneously elevated PTHrP. Results: 138 cases were identified. Solid organ malignancies made up 82.6% (n=114) of cases, with squamous cell carcinoma (28.2% of total) and adenocarcinomas (27.5%) almost equally as common. Hematological malignancy and benign conditions made up 8.7% (n=12) each. Squamous cell carcinoma of the lung was the single most commonly identified etiology (10.9%). Causes not previously identified included myxoid sarcoma, plasma cell leukemia, duodenal adenocarcinoma, metastatic Merkel cell carcinoma and epithelioid hemangioendothelioma. Median survival was different between groups (52 days [interquartile range - IQR - 21-132] for solid organ malignancy, 362 days [18-652] for hematological malignancy, 906 days [16-undefined] for apparently benign group (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001)). There were no differences in PTHrP between the groups. While mean corrected calcium was lower in the benign group (3.03 [2.80-3.29mmol/L)] compared with the solid organ (3.11 [2.89-3.46] mmol/L) and hematological malignancy groups (3.60 [3.01-3.79] mmol/L, p=0.046), it was not a useful discriminator of etiology. Conclusion: PTHrP-mediated hypercalcemia is most frequently caused by solid organ malignancy and it portends a poor prognosis. Although solid organ malignancy had the shortest survival, hematological malignancy and apparently benign causes still had relatively short overall survival.

$Research paper thumbnail of Single-Dose Intravenous Pamidronate Is Effective Alternative Therapy for Paget’s Disease Refractory to Calcitonin$

Hormone Research, 1991

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusi... more We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.

Hormone Research, 1993

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhib... more In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.

Equine Veterinary Journal, 2000

Clinical Endocrinology, 1983

Thyroid function and serum thyroglobulin levels were studied in 66 subjects whose Hodgkin&#39... more Thyroid function and serum thyroglobulin levels were studied in 66 subjects whose Hodgkin's disease had been previously treated by cervical, mediastinal and axillary lymph node (mantle) irradiation. Three patients were already undergoing treatment for thyroid disorders (one for primary hypothyroidism, two for Graves' disease) and a fourth was found to have euthyroid Graves' disease. 36 (Group I) of the remaining 62 patients had normal free thyroxine indices, normal basal thyrotrophin (TSH) levels and normal TSH response to thyrotrophin releasing factor (TRH). In 20 patients (Group II) free thyroxine indices were normal but either basal TSH levels were raised or normal basal TSH levels were associated with an exaggerated response to TRH. In 6 patients (Group III) free thyroxine indices were subnormal. Although results of thyroid function tests in group I lay within the normal range, the mean free thyroxine index was significantly lower and mean basal and peak TSH levels were significantly higher than those of a group of 35 normal subjects, indicating mild thyroid hypofunction. Elevated thyroglobulin levels were demonstrated in 11 irradiated subjects (18%). Mean thyroglobulin levels were significantly raised in each of the three groups of irradiated subjects. Significant positive correlations were found between log serum thyroglobulin and log basal TSH (r = 0.453, P less than 0.001) and log peak TSH (r = 0.515, P less than 0.001) levels. Mild thyroid hypofunction is common after mantle irradiation for Hodgkin's disease and raised serum thyroglobulin levels are a sensitive indicator of TSH stimulation of the damaged thyroid gland.

Clinical Endocrinology, 1990

We studied interrelationships between maternal and neonatal thyroid function, TSH receptor bindin... more We studied interrelationships between maternal and neonatal thyroid function, TSH receptor binding inhibiting immunoglobulins (TBII), and dose of thionamide antithyroid drugs in 44 women with active Graves&amp;#39; disease presenting during 46 pregnancies, and their 48 infants. The women were treated with propylthiouracil (PTU) or carbimazole (CBZ). In 30 pregnancies (30 infants) treatment was withdrawn from 3 to 18 weeks before delivery (Group A). Drug treatment (PTU, n = 10, dose 50-400 mg/day or CBZ, n = 6, dose 5-45 mg/day) was continued throughout pregnancy and delivery in 16 pregnancies producing 18 infants (Group B). The maternal TBII at delivery was well correlated with maternal free thyroxine index (FTI) averaged over the third trimester (r = 0.603, P less than 0.001) and umbilical venous serum TBII (r = 0.940, P less than 0.001). Neonatal FTI was independently related to umbilical vein TBII (t = 2.29, P = 0.03) and maternal dose of antithyroid drug (t = -2.21, P = 0.03). Neonatal thyrotoxicosis was seen in all four infants (8% of births) of women whose TBII levels at delivery exceeded 70%. No child was born with a subnormal FTI but 7/18 infants in group B had raised TSH at birth. This was more likely to occur (P = 0.05) if maternal TBII was less than 30% (6/10) than if maternal TBII was greater than 30% (1/8). Four Group B women with FTI in the lower half of the reference range delivered infants with raised TSH compared with 3/14 (21%) women whose FTI was in the upper half of the reference range or above (P = 0.05). In pregnant women with active Graves&amp;#39; disease TBII levels reflect stimulatory TSH receptor antibody activity. TBII measurements are of use in the prediction of neonatal thyrotoxicosis and impaired neonatal thyroid function in infants of women treated with antithyroid drugs.

Clinica Chimica Acta, 1982

1. Clin Chim Acta. 1982 Jul 15;122(3):419-23. Extraction of steroids from plasma with reversed ph... more 1. Clin Chim Acta. 1982 Jul 15;122(3):419-23. Extraction of steroids from plasma with reversed phase C18 cartridges. Cannell GR, Galligan JP, Mortimer RH, Thomas MJ. PMID: 7105425 [PubMed - indexed for MEDLINE]. MeSH Terms. ...

Journal of Clinical Endocrinology & Metabolism, 1996

Placental deiodination of T, to rT, has been proposed as the factor controlling materno-fetal tra... more Placental deiodination of T, to rT, has been proposed as the factor controlling materno-fetal transmission of T,. We investigated T, transfer in the isolated perfused human placental lobule with and without addition of the deiodinase inhibitor, iopanoic acid. T, (150 nmol/L) in protein-free medium was added to the maternal circuit.