Hypercalcaemia is a common medical problem, can be a manifestation of many diseases and, when severe, can represent a life-threatening medical emergency. Making the correct diagnosis is important to ...prevent unnecessary investigations and parathyroidectomies. At Sultan Qaboos University Hospital, Oman, we have recently seen five patients with severe hypercalcaemia (calcium ≥3.5 mmol/L), most of whom had been misdiagnosed for months or even years. The clinical examination, evaluation of the fasting serum calcium, phosphate, creatinine and 24-hour urine calcium levels together with a review of their radiographs accurately predicted the pathophysiology of the disorder and successfully guided our investigative procedures well before the results of hormone assays became available.
Multiple bone metastases from a differentiated thyroid cancer are usually incurable. We report the case of a young Omani woman who presented with 8 discrete skeletal lesions three years after a total ...thyroidectomy. Following four ablation doses of I-131 she has remained in clinical and biochemical remission for over five years. An extraordinary aspect of this case was the persistent refusal of her husband to use contraception either for himself or his wife. This resulted in her treatment being delayed for more than 6 years during which time the patient delivered and breastfed four additional healthy babies.
We are seeing a progressive increase in the number of young patients with clinically defined maturity onset diabetes of the young (MODY) having a family history suggestive of a monogenic cause of ...their disease and no evidence of autoimmune type 1 diabetes mellitus (T1DM). The aim of this study was to determine whether or not mutations in the 3 commonest forms of MODY, hepatic nuclear factor 4α (HNF4α), HNF1α and glucokinase (GK), are a cause of diabetes in young Omanis.
The study was performed at Sultan Qaboos University Hospital (SQUH), Oman. Twenty young diabetics with a family history suggestive of monogenic inheritance were identified in less than 18 months; the median age of onset of diabetes was 25 years and the median body mass index (BMI) 29 at presentation. Screening for the presence of autoimmune antibodies against pancreatic beta cells islet cell antibody (ICA) and glutamic acid decarboxylase (GAD) was negative. Fourteen of them consented to genetic screening and their blood was sent to Prof. A. Hattersley's Unit at the Peninsular Medical School, Exeter, UK. There, their DNA was screened for known mutations by sequencing exon 1-10 of the GCK and exon 2-10 of the HNF1α and HNF4α genes, the three commonest forms of MODY in Europe.
Surprisingly, none of the patients had any of the tested MODY mutations.
In this small sample of patients with clinically defined MODY, mutations of the three most commonly affected genes occurring in Caucasians were not observed. Either these patients have novel MODY mutations or have inherited a high proportion of the type 2 diabetes mellitus (T2DM) susceptibility genes compounded by excessive insulin resistance due to obesity.
In Oman, many hypertensive patients with a family history of the disease respond to treatment with spironolactone, a mineralocorticoid receptor (MC-R) blocking agent thus suggesting a high prevalence ...of mineralocorticoid (MC) induced disease. The aim of this study was to document the prevalence of MC induced disease in patients with a positive family history of hypertension (HTN).
Serum calcium, potassium, creatinine, aldosterone and renin levels were measured under standard conditions in all patients together with an abdominal ultrasound scan and an adrenal computed tomography (CT) scan in four patients.
In this small study, we show that 18 of the 27 patients (66%) had undetectable (suppressed) renin levels with usually normal aldosterone values (14 patients) and respond to treatment with spironoactone.
We suggest that MC induced hypertension is likely to be common in the Middle East. In evolutionary terms, this makes sense as the ability to conserve salt in hot climates might be expected to confer a definite survival advantage.
In a randomized prospective study, we compared the efficacy of low dose (1073 MBq) and high dose (3700 MBq) iodine-131 administration in postoperative ablation of residual functioning thyroid tissue ...in 63 patients with differentiated thyroid cancer. We were unable to demonstrate any difference between the low- and the high-dose of radioactive iodine in scintigraphic ablation of remnant tissue. In 81% (21/26) of the patients, 1073 MBq ablated after the first dose, 77% (21/26 + 3/5 = 24/31) after the first plus second dose, and 69% (24/31 + 0/4 = 24/35) after the first, second, and third dose. Radioiodine (3700 MBq) ablated in 84%, 73%, and 69% of the patients after respectively 1., 1. plus 2., and 1. plus 2. plus 3. dose. Forty percent of the patients ablated with the low dose and 44% ablated with the high dose had elevated thyroglobulin levels at the time of complete scintigraphic ablation. In conclusion, we did not find any difference between 3700 MBq and 1073 MBq iodine-131 as regard to number of doses needed for complete scintigraphic ablation of residual functioning thyroid tissue.
AIMS
To compare the efficacy of remnant ablation following a single low dose (specific activity of 131I administered, 1074–1110 MBq) vs. a single high dose (mostly 2775–3700 MBq) of 131I in patients ...with differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome.
METHODS
Nineteen studies have reported the results of low dose 131I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near‐total NT; Woodhouse1 vs. sub‐total ST; Woodhouse2). There were 518 low dose and 449 high dose patients in all.
RESULTS
The average failure of a single low dose was 46 ± 28% (SD). Meta‐analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near‐total as opposed to sub‐total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05).
CONCLUSION
High dose 131I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose 131I (2775–3700MBq) for ablation of the remnant.
To compare the efficacy of remnant ablation following a single low dose (specific activity of
I administered, 1074-1110 MBq) vs. a single high dose (mostly 2775-3700 MBq) of
I in patients with ...differentiated thyroid cancer and to determine whether or not the extent of surgery influences outcome.
Nineteen studies have reported the results of low dose
I ablation. Of these, 11 met our criteria for a comparative analysis. Two additional cohorts of ours were added and these were analysed in two groups based on the extent of surgery (near-total NT; Woodhouse1 vs. sub-total ST; Woodhouse2). There were 518 low dose and 449 high dose patients in all.
The average failure of a single low dose was 46 ± 28% (SD). Meta-analysis revealed a statistically significant advantage for a single high over a single low dose and a pooled reduction in relative risk of failure of the high dose of about 27% (P < 0.01). From this we estimate that for every seven patients treated one more would be ablated given a high rather than a low dose (assuming a low dose failure risk of 50%). Also, a significantly greater proportion of patients are ablated after a single high or low dose, if they underwent near-total as opposed to sub-total thyroidectomy (summary relative risk (RR) 1.4; P < 0.05).
High dose
I is more efficient than low dose for remnant ablation particularly after less than total thyroidectomy. Results suggest that patients with differentiated thyroid cancer should routinely have a total thyroidectomy followed by high dose
I (2775-3700MBq) for ablation of the remnant.
Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. To identify common PrCa susceptibility alleles, we conducted a multi-stage genome-wide association study ...and previously reported the results of the first two stages, which identified 16 novel susceptibility loci for PrCa. Here we report the results of stage 3 in which we evaluated 1,536 SNPs in 4,574 cases and 4,164 controls. Ten novel association signals were followed up through genotyping in 51,311 samples in 30 studies through the international PRACTICAL consortium. In addition to previously reported loci, we identified a further seven new prostate cancer susceptibility loci on chromosomes 2p, 3q, 5p, 6p, 12q and Xq (
P
=4.0 ×10
−8
to
P
=2.7 ×10
−24
). We also identified a SNP in
TERT
more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ~25% of the familial risk in this disease, have now been identified.
To investigate the effects of bromocriptine withdrawal during one or more pregnancies in patients who presented with pituitary macroprolactinomas with suprasellar extension.
Four infertile patients ...presenting with a macroprolactinoma with suprasellar extension conceived during treatment with bromocriptine on 10 occasions resulting in eight full-term normal deliveries. Treatment was withheld shortly after conception in each pregnancy.
Serum prolactin (PRL) levels fell initially from a mean of 2,776 (range 1,682 to 4,515) to 27 micrograms/L (range 1 to 71) with the development of a partially empty sella in all patients. Recovery of visual field defects occurred in the only affected individual. In case 1, PRL levels remained within the normal range, after bromocriptine withdrawal in the first pregnancy, with the development of an empty sella. Prolactin levels, however, increased substantially in cases 2 to 4. An asymptomatic suprasellar tumor extension returned in cases 2 and 3. After two or more pregnancies (cases 1, 3, and 4), there was a progressive decline in the serum PRL levels. Although still elevated in cases 3 and 4, the PRL levels were considerably below those obtained at presentation or in the first pregnancy. Tumor regression with the development of an empty sella was observed in both these patients as well in their pregnancy or postpartum period.
Bromocriptine may be safely withdrawn during pregnancy in patients presenting with a macroprolactinoma. With multiple bromocriptine induced pregnancies, PRL levels and tumor size may progressively decrease with the eventual development of an empty sella.
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