Experience of X-linked hypophosphatemic rickets in the Gulf Cooperation Council countries: case series.

Summary: X-linked hypophosphatemic rickets (XLH), the most prevalent form of inherited hypophosphatemic rickets, is caused by loss-of-function mutations in the gene encoding phosphate-regulating endopeptidase homolog, X-linked (PHEX). This case series presents 14 cases of XLH from Gulf Cooperation Council (GCC) countries. The patients' medical history, biochemical and radiological investigative findings, as well as treatment responses and side effects from both conventional and burosumab therapy, are described. Cases were aged 2-40 years at diagnosis. There were two male cases and 12 female cases. All cases were treated with conventional therapy which resulted in a lack of improvement in or worsening of the clinical signs and symptoms of rickets or biochemical parameters. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients' quality of life and adherence to treatment. In the 10 patients treated with burosumab, there was a marked improvement in the biochemical markers of rickets, with a mean increase in serum phosphate of +0.56 mmol/L and tubular maximum phosphate reabsorption (TmP) to glomerular filtration rate (GFR) ratio (TmP/GFR) of +0.39 mmol/L at 12 months compared to baseline. Furthermore, a mean decrease in serum alkaline phosphatase (ALP) of -80.80 IU/L and parathyroid hormone (PTH) of -63.61 pmol/L at 12 months compared to baseline was observed in these patients. Additionally, patients treated with burosumab reported reduced pain, muscle weakness, and fatigue as well as the ability to lead more physically active lives with no significant side effects of treatment. Learning points: Conventional therapy resulted in a suboptimal response, with a lack of improvement of clinical signs and symptoms. Side effects of conventional therapy included nausea, diarrhea, abdominal pain, nephrocalcinosis, and hyperparathyroidism, which affected the patients' quality of life and adherence to treatment. Burosumab demonstrated marked improvements in the biochemical markers of rickets, in addition to reducing pain, muscle weakness, and fatigue. There were no significant side effects associated with burosumab therapy.

A Practical Approach to the Management of Residual Cardiovascular Risk: United Arab Emirates Expert Consensus Panel on the Evidence for Icosapent Ethyl and Omega-3 Fatty Acids.

PURPOSE: Patients with hyperlipidemia treated with statins remain at a residual cardiovascular (CV) risk. Omega-3 polyunsaturated fatty acids hold the potential to mitigate the residual CV risk in statin-treated patients, with persistently elevated triglyceride (TG) levels. METHOD: We reviewed the current evidence on the use of icosapent ethyl (IPE), an omega-3 fatty acid yielding a pure form of eicosapentaenoic acid. RESULTS: REDUCE-IT reported a significant 25% reduction in CV events, including the need for coronary revascularization, the risk of fatal/nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and CV death in patients on IPE, unseen with other omega-3 fatty acids treatments. IPE was effective in all patients regardless of baseline CV risk enhancers (TG levels, type-2 diabetes status, weight status, prior revascularization, or renal function). Adverse events (atrial fibrillation/flutter) related to IPE have occurred mostly in patients with prior atrial fibrillation. Yet, the net clinical benefit largely exceeded potential risks. The combination with other omega-3 polyunsaturated fatty acids, in particular DHA, eliminated the effect of EPA alone, as reported in the STRENGTH and OMEMI trials. Adding IPE to statin treatment seems to be cost-effective, especially in the context of secondary prevention of CVD, decreasing CV event frequency and subsequently the use of healthcare resources. CONCLUSION: Importantly, IPE has been endorsed by 20 international medical societies as a statin add-on treatment in patients with dyslipidemia and high CV risk. Robust medical evidence supports IPE as a pillar in the management of dyslipidemia.

Granulomatous hypophysitis: rare disease with challenging diagnosis.

Granulomatous hypophysitis is rare pathology that mimics pituitary adenoma. Diagnosis is only confirmed by histopathology examination. Trans-sphenoidal surgery is considered diagnostic when descent tissue specimen is obtained and therapeutic by decompressing optic pathway and the sella. Pathological findings always reveal granulomatous areas, multinucleated giant cells, plasma cells, and lymphocytes.

Driving and diabetes mellitus in the Gulf Cooperation Council countries: Call for action.

The aim of the present article is to increase awareness concerning safe driving for patients with diabetes in the Gulf Cooperation Council (GCC) countries and to provide recommendations concerning the management of these patients. The cognitive, motor, and sensory skills required for driving can be adversely affected by diabetes as well as the side effects of anti-diabetic medications, particularly hypoglycemia. The prevalence of diabetes in the GCC countries is among the highest in the world. As the number of diabetic drivers in these countries continues to increase, the number at risk of having a motor vehicle accident is also expected to increase. We reviewed the available literature concerning driving and diabetes, particularly in relation to the current situation in the GGC countries. Unfortunately, very little published information is available addressing this issue in the GCC countries. Most of the GCC countries lack legislation on driving and diabetes. We have proposed recommendations to help diabetic drivers in the GCC countries as well as to provide guidance to health care professionals managing these patients.

Spontaneous recovery of adrenal insufficiency in POEMS syndrome.

POEMS syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. We report the first case of spontaneous recovery of adrenal insufficiency in a patient with POEMS syndrome treated with autologous hematopoietic cell transplantation. We conclude that in patients with POEMS syndrome, adrenal insufficiency should be regularly assessed for potential recovery.

Spontaneous singleton and twin pregnancy in two patients with polycystic ovary syndrome and type 2 diabetes following treatment with metformin combined with rosiglitazone.

Two women, a Saudi Arab and a Caucasian, aged 28 and 41 years, had a long history of polycystic ovary syndrome (PCOS) and primary infertility, which was refractory to various treatment modalities. Both later developed type 2 diabetes, managed initially with metformin; rosiglitazone was added later to improve glycaemic control. Both conceived spontaneously, resulting in singleton and twin pregnancies giving birth to healthy babies. The combination of rosiglitazone with metformin may result in improved fertility with ovulation and spontaneous conception in women with PCOS and type 2 diabetes. Randomized controlled trials are needed to assess the feasibility of this combination to improve fertility in women with PCOS. However, in the absence of any safety data, those women, following counselling, should be warned against the possibility of spontaneous pregnancy and contraceptive measures should be discussed and offered where appropriate.

The low-dose ACTH test does not provide a useful assessment of the hypothalamic-pituitary-adrenal axis in secondary adrenal insufficiency.

OBJECTIVE: The 1 microg ACTH stimulation test has been introduced to improve the sensitivity of ACTH as a test of the integrity of hypothalamic-pituitary-adrenal axis (HPAA). This study aims to compare the sensitivity, specificity and diagnostic accuracy of the "low-dose" 1 microg ACTH (LDACTH) test and the "standard dose" 250 microg ACTH (SDACTH) test, with the overnight metyrapone test (OMT) which assesses the entire HPAA. DESIGN: A prospective evaluation of the performance of SDACTH and LDACTH screening tests in a diverse cohort of patients with possible adrenal insufficiency as routinely encountered in clinical practice using the OMT as the reference method. PATIENTS: A total of 51 patients (26 with asthma on inhaled glucocorticoid, nine with hypopituitarism, three with hypothyroidism, one with hyponatraemia, one with Crohn's disease, one with encephalitis and 10 with non-specific symptoms) each underwent SDACTH, LDACTH and OMT tests in random sequence at least 1 week apart. MEASUREMENTS: Blood was sampled for plasma cortisol levels at 0 and 30 min after intravenous administration of 1 microg and 250 microg of ACTH. Metyrapone 30 mg/kg body weight was taken orally at midnight, and plasma samples were taken for measurement of 11-deoxycortisol and cortisol next morning between 08.00 and 09.00 h. The OMT was deemed to be abnormal when both 11-deoxycortisol and cortisol levels were less than 200 nmol/l. RESULTS: The sensitivity and specificity at an empirical "normal" plasma cortisol threshold value of 500 nmol/l were 67% and 100% for the SDACTH test, and 73% and 81% for the LDACTH test, respectively. As the plasma cortisol cut-off value was increased to 550 nmol/l and 600 nmol/l, the sensitivity of the SDACTH test was 67% and 80% and specificity was 97% and 92%, respectively. The sensitivity of the LDACTH test increased from 93% at plasma cortisol cut-off value of 550 nmol/l to 100% at plasma cortisol cut-off value of 600 nmol/l. However, the specificity of the LDACTH test fell from 72% to 56% as the plasma cortisol cut-off value was increased from 550 nmol/l to 600 nmol/l. A receiver operating characteristic curve demonstrated that the specificity of the SDACTH test was higher than the specificity of the LDACTH test at any given level of sensitivity. CONCLUSIONS: Both the LDACTH and SDACTH tests fail to achieve acceptable levels of sensitivity and specificity to be useful as screening tests for secondary adrenal insufficiency. In this context the OMT can be safely used to assess the integrity of the entire HPAA.