A Case Report of 17α-Hydroxylase Deficiency in Two Saudi Siblings With Different Karyotyping.

Congenital adrenal hyperplasia (CAH) consists of variable disorders of sex determination and differentiation. 17α-hydroxylase deficiency (17OHD) is an uncommon form of those disorders, which is typically characterized by hypertension, hypokalemia, failure of puberty, and ambiguous genitalia. The 17α-hydroxylase enzyme is encoded by the CYP17A1 gene and it is required for the synthesis of cortisol and sex steroids. The affected females with 17OHD usually present with primary amenorrhea and delayed puberty, which are associated with hypertension and hypokalemia while male patients might show female external genitalia, pseudohermaphroditism, or variable degrees of ambiguous genitalia with intra-abdominal testes in addition to hypertension and hypokalemia as well. We present two Saudi siblings (19 and 16 years old) who were diagnosed with the rare CAH subtype of 17OHD after presenting with long-standing hypertension, refractory hypokalemia, and failure of puberty. It is interesting that both siblings had biochemical primary adrenal insufficiency; however, both patients did not clinically present with an acute adrenal crisis, which is likely due to the effect of increased levels of deoxycorticosterone. Additionally, although both patients have similar phenotypes and clinical presentations, they have different karyotypes. This again highlights the variability of the manifestations that can result from 17OHD even with an identical mutation in the same family. Both patients were treated successfully with dexamethasone, which has led to the normalization of hypertension, resolution of hypokalemia, and discontinuation of anti-hypertensive medications and potassium supplements after several years of treatment. However, the entire management is quite challenging and requires a multidisciplinary approach regarding difficult issues such as gender identity and assignment and fertility issues in addition to a life-long follow-up.

Clinical Features, Therapeutic Trends, and Outcome of Giant Prolactinomas: A Single-Center Experience Over a 12-Year Period.

BACKGROUND: Management of giant prolactinomas presents a different challenge than the management of traditional prolactinomas. OBJECTIVE: The aim of this study was to report the largest long-term single-center study of giant prolactinomas to analyze their clinical features; define epidemiological characteristics, comorbidities, complications, treatment outcomes; and to demonstrate our experience with long-term cabergoline (CAB) treatment of these giant tumors. METHODS: A retrospective case study and clinical review of patients presenting with giant prolactinomas in the pituitary clinic at King Fahad Medical City (KFMC), Riyadh, Saudi Arabia, in the period between 2006 and 2018 were included in the study. Of the charts reviewed, 33 patients (24 men; 9 women) with age of diagnosis between 18 and 63 years (mean = 37.21 years) met the selection criteria for giant prolactinomas. RESULT: The most common presenting features include headache (87.8%), visual defects (69.7%), and hypogonadism (51.5%). The baseline means serum prolactin (PRL) level was extremely high for both sexes (95 615.03 nmol/L), which eventually decreased by as much as 95.4% after CAB treatment. Serum PRL concentrations completely normalized in 11 patients and significantly reduced in 22 patients. The mean tumor volume at baseline was 42.87 cm3, whereas the mean posttreatment tumor volume was 3.42 cm3 (no residual tumor in 2 patients, while in others, it ranged from 0.11 to 16.7 cm3) at the last follow-up visit. The mean change in tumor volume was 88.84%. Tumor volume decreased by an average of 92% for men and 80.4% for women. One patient had no tumor size change with CAB (3.5 mg thrice a week) or radiotherapy and required surgery. The response rate (remission after medical therapy alone) in this series was 84.84%. CONCLUSIONS: Findings reinforce results from our previous study that CAB provides dramatic clinical improvements with an excellent safety profile. The CAB should, therefore, be considered as the primary therapy for giant prolactinomas.

Association of Glycosylated Hemoglobin Levels With Vitamin D Status.

BACKGROUND: The discovery of vitamin D is one of medicine's great achievements. Despite all the positive evidence emerging about the beneficial effect of vitamin D, we still find many are vitamin D deficient. The purposes of this study were to examine the association between serum 25-hydroxyvitamin D (25(OH)D) and glycosylated hemoglobin (HbA1c) levels, to test the hypothesis that lower 25(OH)D levels are associated with poorer glucose control in diabetes mellitus (DM) patients and to investigate the effect of vitamin D supplementation on HbA1c levels. METHODS: This was a prospective observational cohort study of all patients with type 1 and type 2 diabetes (above 12 years) who attended the outpatient clinics of a tertiary center in Riyadh. HbA1c and vitamin D levels were recorded prior to supplementation and after 9 months of supplementation with vitamin D. All patients were divided into four groups according to their vitamin D level and an association between 25(OH)D and HbA1c was tested. RESULTS: Results showed that 73.1% of the patients had 25(OH)D levels < 50 nmol/L. We observed lowering of HbA1c after vitamin D supplementation (from mean HbA1c of 10.55 to 7.70). We found HbA1c to be inversely related to serum vitamin D levels (r = -0.14 (P < 0.0000002) before supplementation and -0.16 (P < 0.000001) after supplementation with vitamin D). CONCLUSIONS: Advising patients with higher HbA1c to test their vitamin D level and correct any deficiency will result in better blood glucose control and benefit the patient's overall health.

Glycemic control and pregnancy outcomes in patients with diabetes in pregnancy: A retrospective study.

CONTEXT: Diabetes in pregnancy (DIP) is either pregestational or gestational. AIMS: To determine the relationship between glycemic control and pregnancy outcomes in a cohort of DIP patients. SETTINGS AND DESIGN: In this 12-month retrospective study, a total of 325 Saudi women with DIP who attended the outpatient clinics at a tertiary center Riyadh, Saudi Arabia, were included. SUBJECTS AND METHODS: The patients were divided into two groups, those with glycated hemoglobin (HbA1c) ≤6.5% (48 mmol/mol) and those with glycated hemoglobin (HbA1c) above 6.5%. The two groups were compared for differences in maternal and fetal outcomes. STATISTICAL ANALYSIS USED: Independent Student's t-test and analysis of variance were performed for comparison of continuous variables and Chi-square test for frequencies. Odds ratio and 95% confidence intervals were calculated using logistic regression. RESULTS: Patients with higher HbA1c were older (P = 0.0077), had significantly higher blood pressure, proteinuria (P < 0.0001), and were multiparous (P = 0.0269). They had significantly shorter gestational periods (P = 0.0002), more preterm labor (P < 0.0001), more perineal tears (P = 0.0406), more miscarriages (P < 0.0001), and more operative deliveries (P < 0.0001). Their babies were significantly of greater weight, had more Neonatal Intensive Care Unit (NICU) admissions, hypoglycemia, and macrosomia. CONCLUSIONS: Poor glycemic control during pregnancy is associated with adverse maternal and fetal outcomes (shortened gestational period, greater risk of miscarriage, increased likelihood of operative delivery, hypoglycemia, macrosomia, and increased NICU admission). Especially at risk are those with preexisting diabetes, who would benefit from earlier diabetes consultation and tighter glycemic control before conception.

Carbonic Anhydrase II Deficiency in a Saudi Woman.

OBJECTIVE: Carbonic anhydrase (CA) II deficiency is a rare autosomal recessive disorder caused by mutation in the CA II gene that leads to osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification. Our aim is to present a patient with the classic triad of CA II deficiency syndrome to enhance the awareness about this rare syndrome. METHODS: We describe the clinical and radiological findings of a Saudi woman patient with CA II deficiency syndrome. RESULTS: A Saudi woman in her 20s presented to our hospital for evaluation of increased bone density. She was known to have delayed developmental milestone with growth retardation and poor scholastic performance. She had multiple fragile fractures started at the age of 15 involving the lower extremities. A physical examination revealed dysmorphic features and intellectual disability with intelligence quotient (IQ) of 36. The initial blood workup showed a picture of distal RTA with hypokalemia, and the radiological imaging confirmed the presence of osteopetrosis and multiple kidney stones. The combination of osteopetrosis with RTA raised the possibility of CA II deficiency. Therefore, computed tomography (CT) of the brain was done and showed intracranial calcification involving the basal ganglia. She was started on potassium chloride and sodium bicarbonate. In addition, she underwent right-sided percutaneous nephrolithotripsy. Her DNA analysis came to show a sequence variant c.232+1G>A, which was detected in both of the CA II genes (homozygous). CONCLUSION: Early recognition of the disease is a key, as an early appropriate treatment institution is essential in order to prevent further complications.