Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.

BACKGROUND: Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. METHODS: This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. RESULTS: Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339-6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. CONCLUSION: This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

Novel mutations in PDE6A and CDHR1 cause retinitis pigmentosa in Pakistani families.

AIM: To investigate the genetic basis of autosomal recessive retinitis pigmentosa (arRP) in two consanguineous/ endogamous Pakistani families. METHODS: Whole exome sequencing (WES) was performed on genomic DNA samples of patients with arRP to identify disease causing mutations. Sanger sequencing was performed to confirm familial segregation of identified mutations, and potential pathogenicity was determined by predictions of the mutations' functions. RESULTS: A novel homozygous frameshift mutation [NM_000440.2:c.1054delG, p. (Gln352Argfs*4); Chr5:g.149286886del (GRCh37)] in the PDE6A gene in an endogamous family and a novel homozygous splice site mutation [NM_033100.3:c.1168-1G>A, Chr10:g.85968484G>A (GRCh37)] in the CDHR1 gene in a consanguineous family were identified. The PDE6A variant p. (Gln352Argfs*4) was predicted to be deleterious or pathogenic, whilst the CDHR1 variant c.1168-1G>A was predicted to result in potential alteration of splicing. CONCLUSION: This study expands the spectrum of genetic variants for arRP in Pakistani families.

USH2A gene variants cause Keratoconus and Usher syndrome phenotypes in Pakistani families.

BACKGROUND: Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy, affecting approximately 1 in 4000 individuals worldwide. The most common form of syndromic RP is Usher syndrome (USH) accounting for approximately 20-30 % of RP cases. Mutations in the USH2A gene cause a significant proportion of recessive non-syndromic RP and USH type II (USH2). This study aimed to determine the causative role of the USH2A gene in autosomal recessive inherited ocular diseases and to establish genotype-phenotype correlation associated with USH2A variants. METHODS: We performed direct Sanger sequencing and co-segregation analysis of the USH2A gene to identify disease causing variants in a non-syndromic RP family, two USH2 families and two Keratoconus (KC) families. RESULTS: Disease causing variants in the USH2A gene were identified in two families displayed KC and USH2 phenotypes. A novel variant c.4029T > G, p.Asn1343Lys in the USH2A gene was detected in a Pakistani family with KC phenotype. In addition, a missense variant (c.7334 C > T, p. Ser2445Phe) in the USH2A gene was found segregating in another Pakistani family with USH2 phenotype. Homozygosity of identified missense USH2A variants was found associated with autosomal recessive inherited KC and USH2 phenotypes in investigated families. These variants were not detected in ethnically matched healthy controls. Moreover, the USH2A variants were predicted to be deleterious or potentially disease causing by PolyPhen-2, PROVEAN and SIFT. CONCLUSIONS: This study provided first evidence for association of a novel USH2A variant with KC phenotype in a Pakistani family as well as established the phenotype-genotype correlation of a USH2A variant (c.7334 C > T, p. Ser2445Phe) with USH2 phenotype in another Pakistani family. The phenotype-genotype correlations established in present study may improve clinical diagnosis of affected individuals for better management and counseling.

Trace metal profiling in patients with depression in Pakistani population.

OBJECTIVE: To determine level of trace metals in patients with depression in order to explore any association between the two. METHODS: The case-control study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology and Armed Forces Institute of Mental Health, Rawalpindi, Pakistan, from January to December 2017, and comprised diagnosed cases of depression with equal number of age- and gender-matched controls. Depression was diagnosed by a consultant psychiatrist as per the International Classification of Diseases version 10 / Diagnostic and Statistical Manual of Mental Disorders -IV criteria and a self-reported depression screening through Siddiqui-Shah Depression Scale. Blood samples were collected from each subject for the measurement of metals like zinc, chromium and copper. Data was analysed using SPSS 24. RESULTS: Of the 370 subjects, there were 185(50%) in each of the two groups. There were 82(44.3%) males and 103(55.7%) females among the cases with an overall mean age of 37.75±11.49 years, and 65(35.1%) males and 120(64.9%) females with an overall mean age of 39.38±12.56 years among the controls. Mean levels of zinc and copper were significantly different between the groups (p<0.05), while the difference was non-significant for chromium (p>0.05). Equivocal prevalence of depression was present between males and females (p=0.04) without any significant age group association (p=1.92). CONCLUSIONS: Blood level of serum zinc and copper were found to be associated with depression.

Wastage of Blood Units at Tertiary Care Hospitals of Lahore.

INTRODUCTION:  Blood and its products are the most valuable resource in every healthcare institution. Judicial use of these limited resources is necessary and important to maintain sufficient supply. Blood products and its transfusion system are being evaluated by the use of several markers. The use of crossmatch to transfusion ratio (C/T) was first proposed by Boral Henry in 1975. Nowadays, the C/T ratio is being used by researchers to assess transfusion practices. Ideally, (C/T) ratio has to be 1.0 but it has been suggested that a ratio of 2.5 or less would indicate effective blood use. OBJECTIVE: To assess crossmatch to transfusion ratio (C/T ratio), transfusion probability (%T), and transfusion index (TI) in patients of medical and surgical wards. To assess the wastage of blood components/whole blood units. METHODS:  A cross-sectional study was conducted at Mayo Hospital/King Edward Medical University, Lahore, Services Hospital Lahore, and Alkhidmat Blood Bank Surrayya Azeem Hospital between January 2019 and June 2019. Nonprobability convenient sampling was performed and all collected data were entered and analyzed by using statistical package for social sciences (SPSS version 20). RESULTS:  The total patients who were ordered to arrange blood were 1322 for which overall 2715 crossmatches had been done. Among these crossmatches, a total of 1536 of the donors were bled for from which only 815 units had been transfused to the patients. Overall C/T ratio was found to be 3.33 and the overall wastage was 38.9%. CONCLUSIONS:  Blood transfusion is considered useful in the management of surgical as well as medical patients. Too many units are ordered out of which the majority are wasted due to nonutilization. There is a need for standard operating procedures for transfusion of blood. There shall be regular audits to improve the blood collection, treatment, delivery, and usage practices of this scarce resource.

Risk Stratification of Chronic Myeloid Leukemia According to Different Prognostic Scores.

Introduction Several prognostic indices are in use to stratify chronic myeloid leukemia (CML) patients: Sokal, Hasford, and the European Treatment and Outcome Study (EUTOS) being the most commonly reported ones. The application of different scores may cause variability in the determination of disease prognosis. This study was conducted to stratify patients of CML in accordance with Sokal, Hasford, and EUTOS scoring systems and to determine the concordance rate of risk categories, calculated by using all three scoring systems. Methods This study was conducted at King Edward Medical University from January 2013 to May 2019. A total of 114 patients were diagnosed with CML in the chronic phase during the study period and included in the analysis. Variables of interest were computed using Microsoft Excel. These variables include age, spleen size, platelet count, the percentage of myeloblasts in the peripheral blood, as well as the percentage of basophils and eosinophils in the peripheral blood. Using these baseline variables, the prognostic category of each patient was calculated using Sokal, Hasford, and EUTOS scores. Results The male to female ratio of patients included in the study was 1.43. The mean age was 39.3±1.58 years, with an age range of 13 to 95 years. A total of only 4 out of 73 patients were categorized as a low-risk category, whereas 23 out of 80 patients were categorized into a high-risk category by all three scoring systems. The assignment of prognostic categories was variable, depending on which prognostic score was applied. The concordance rate of Sokal vs Hasford was 53%, Sokal vs EUTOS 64%, and Hasford vs EUTOS 98%. Conclusion There is considerable inter-variability between the various prognostic indicators. In general, the Hasford and EUTOS scores assign some patients to a lower risk category when compared to Sokal score.

Biochemical spectrum of parathyroid disorders diagnosed at a tertiary care setting.

OBJECTIVE: To determine the clinical and biochemical pattern of parathyroid disorders in a tertiary care setting.. METHODS: The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from September 2017 to February 2018, and comprised patients with suspected parathyroid disorders. A panel of biochemical tests were used for diagnosis of parathyroid disorders, which included parathyroid hormone levels, total calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, magnesium, total vitamin D and urinary calcium-to-creatinine ratio. SPSS 24 was used for data analysis. RESULTS: Of the 384 subjects, 248(65%) were male and 136(35%) were female. Overall mean age was 48±19years. Of the total, 302(786%) had parathyroid issues, with 244(81%) having secondary hyperparathyroidism. Mean serum total calcium, phosphorus, ionized calcium, magnesium and total vitamin D were 8.98±1.52 mg/dl, 4.0±1.30 mg/dl, 4.65±0.52 mg/dl, 2.11±0.27 mg/dl and 20.5±8.52 ngml respectively. Of the patients diagnosed with secondary hyperparathyroidism, 72.2% patients had chronic kidney disease and 20.2% had isolated vitamin D deficiency. CONCLUSIONS: Parathyroid disorders had significant impact on bone health. Moreover, secondary hyperparathyroidism was seen to be emerging as a major endocrine problem, especially in chronic kidney disease patients and vitamin D-deficient individuals.

Diagnostic accuracy of cannabinoid testing by liquid chromatography-tandem mass spectrometry in human hair.

OBJECTIVE: To determine the diagnostic accuracy of Cannabinoids testing by LC-MS/MS in human hair and compare it with urine in civil heavy vehicle drivers. METHODS: Current study was a diagnostic accuracy study done in "Armed Forces Institute of Pathology Rawalpindi, Pakistan" from February to November 2017. Urine and hair samples were collected by non-probability convenient sampling technique from 151 heavy vehicle drivers from Punjab. Hair and urine samples were collected from each subject. Separation of compounds was performed on Agilent Poroshell and analyzed using 6460 Triple Quadrapole LC-MS along-with software Mass hunter ©. RESULTS: Study population (151 civil heavy vehicle drivers) was divided into three main divisions There were 69 (46%) truck drivers,43 (28.5%) twenty-wheeler drivers and 39 (26%) bus drivers. Mean age of study participants was 36±10.82 years. Paired t-test was applied to check mean difference between the two tests' concentration (i.e urine and hair analysis for cannabis) which showed significant difference at p<0.001. Among the different factors of diagnostic accuracy in hair and urine specimens were: Sensitivity (96% and 62%), Specificity (93% and 95%) Positive Predictive Value (88% and 87%), Negative Predictive Value (97% and 82%) respectively. Overall diagnostic accuracy of Cannabinoids detection in hair was 94% while in urine it was 83%. ROC curve showed area under curve of 0.79 and 0.96 for urine and hair samples respectively. CONCLUSIONS: Current study signified hair as a substitute matrix owing to its non-invasive specimen collection, better diagnostic yield and wider detection period compared to urine.

Comparative evaluation of 30 and 60 minutes cortisol levels during short synacthen test for diagnosis of adrenal insufficiency.

OBJECTIVE: To assess and compare diagnostic value of 30-minute cortisol level over 60-minute level in the diagnosis of adrenal insufficiency. METHODS: The comparative cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from August 2017 to May 2018, and comprised patients referred to the facility for short synacthen test with suspicion of adrenal insufficiency. Blood samples for serum cortisol were taken at time-0 and then 30 and 60 minutes after the adreno-cortico-tropic hormone injection. Total serum cortisol was measured. Adrenal insufficiency was defined as stimulated cortisol level <500 nmol/l at 30 and 60 minutes post-stimulation. SPSS 24 was used for data analysis. RESULTS: Of the 111 subjects, 56(50.4%) were males and 55(49.5%) were females. Overall mean age was 34±20 years. Mean basal serum cortisol level was 110±98 nmol/l in patients with adrenal insufficiency and it was 294±164 nmol/l in patients with intact adrenal functions. Cortisol level at both 30 and 60 minutes was significant (p<0.001). Receiver Operating Characteristics curve was plotted which showed area under curve of 0.83 and 0.82 for 60 and 30 minutes respectively. CONCLUSIONS: The 30-minute cortisol level post-stimulation carried no diagnostic value . Measuring cortisol level once at 60-minute post-stimulation would be of more value apart from being cost-effective in the diagnosis of adrenal insufficiency.

Triglycerides-to-HDLC Ratio as a Marker of Cardiac Disease and Vascular Risk Factors in Adults.

OBJECTIVE: To find out correlation of triglycerides-to-HDL cholesterol ratio in elders with cardiac risk factors like obesity, diabetes, and hypertension. STUDY DESIGN: Observational cross-sectional study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Combined Military Hospital, Rawalpindi, from January to June 2018. METHODOLOGY: Inclusion standards were participants aged 20-59 years .Patients with comorbidity and chronic illness were excluded from the study. A planned standardised homogeneous survey was conducted as a pilot study. Social, economic and physical variables like age, gender, marital status and presence of diseases, all were taken into consideration. To check association among cardio metabolic risk factors like diabetes, obesity, hypertension, and TG/HDL-C ratio, Chi-square test was computed for all cardio metabolic risk factors. RESULTS: Overall 350 participants were studied after attainment of authorisation from Ethical Review Board of Combined Military Hospital, Rawalpindi, in which 268 (76.6%) were women; whereas, 82 (23.4%) were men with mean age of 37 ± 11.64 years. There was strong association of TG/HDL ratio with BMI, HOMA-IR, WBISI, visceral fats, smooth muscle mass, HDL, LDL, and triglycerides with p <0.04, p <0.001, p <0.01, and p <0.001, respectively. CONCLUSION: TG/HDLC ratio can be considered as a potential biomarker for the early prediction of cardiometablic risk factors.

Diagnostic accuracy of human chorionic gonadotropins (HCG) stimulation test in XY-disorders of sex development (XY-DSD) presented in Armed Forces Institute of Pathology.

OBJECTIVE: To determine diagnostic accuracy of human chorionic gonadotropins stimulation test in differentiating androgen insensitivity syndrome and 5-alpha reductase deficiency, keeping testosterone to dihydrotestosterone ratio as the gold standard. METHODS: The cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to December, 2016, and comprised patients aged 01 day to 20 years having XY chromosomes on karyotyping and with a spectrum of phenotypes. Blood samples were collected from each subject for basal serum testosterone, serum luteinizing hormone and serum follicular stimulating hormone level. Human chorionic gonadotropins stimulation test was performed in every subject as per the protocol. Sandwich chemiluminescence immunoassay technique was used to analyse serum samples. Serum dihydrotestosterone level was also detected to determine testosterone and dihydrotestosterone ratio. Data was analysed using SPSS 24. . RESULTS: Of the 104 subjects with a mean age of 1.78}0.95 years,96(92.3%) were diagnosed as cases of androgen insensitivity syndrome on the basis of human chorionic gonadotropins stimulation response level, which was 2-9 times of basal serum testosterone level. Also, 8(7.7%) subjects were diagnosed to have 5-alpha reductase deficiency syndrome. In such subjects, post-human chorionic gonadotropins response level of serum testosterone was more than 10 times of the basal level. CONCLUSIONS: The human chorionic gonadotropins stimulation test was found to be comparable to testosterone-to dihydrotestosterone ratio in differentiating between case of androgen insensitivity syndrome and 5-alpha reductase deficiency.

Growth Hormone and ACTH Deficiency in a Diabetic Adult.

Adult growth hormone deficiency (AGHD) syndrome has a constellation of features, like impaired cognitive function, altered body composition, poor quality of life and various metabolic changes. Most of its features resemble signs of aging as growth hormone (GH) secretion decreases with age. Hypothalamic-pituitary-adrenal (HPA) axis should be thoroughly investigated in this disease as patients with AGHD are at risk of life-threatening consequences due to partial or complete ACTH deficiency, especially in stressful conditions. GH deficiency has also been related to diabetes or glucose intolerance. It is relatively underdiagnosed problem in adults and requires a thorough workup including dynamic function tests like insulin tolerance test (ITT), which has been termed as the gold standard for the diagnosis of patients with ACTH deficiency.

A Child with Weight Loss and Alacrimation: Triple A Syndrome.

Triple A syndrome or Allgrove's syndrome is a rare autosomal recessive disorder usually manifested with three main clinical features, i.e. achalasia, alacrimation and adrenal inadequacy. Sometimes, it presents with polyneuropathy and neurological complications. Here, we report a case of a 7-year girl presenting with features of weight loss who was diagnosed with adrenal insufficiency at the age of 7 years while achalasia was diagnosed at the age of 3 years. First manifestation was achalasia and at that time, alacrimation was also defected. A 7-year XX female child presented at Endocrine Clinic of Armed Forces Institute of Pathology (AFIP) with hyperpigmentation, easy fatigue and weight loss. She had one sibling with same complaints and one brother died at the age of 3 years because of adrenal insufficiency. Her laboratory investigations revealed low cortisol level and high ACTH level, with inadequate response as well as short synacthen test (dynamic function test). This is a first case of Allgrove's syndrome reported in a tertiary hospital setting of Pakistan. Allgrove's syndrome should be considered in patients who report with adrenal insufficiency.

A Child with Ambiguous Genitalia: An Atypical Presentation.

Lipoid congenital adrenal hyperplasia (LCAH) (OMIM No. 201710) is the most severe type of congenital adrenal hyperplasia (CAH). Its clinical presentation includes lethal disturbance of adrenal and gonadal steroid synthesis due to impairment in the conversion of cholesterol to pregnenolone. Infants with this disorder experience salt loss, and glucocorticoid and mineralocorticoid deficiencies. Replacement therapy has enabled long-term survival. Classic LCAH is relatively common in Japan and Korea but extremely rare in Caucasian populations. An XY male 5-year-old child presented at Endocrine Clinic of Armed Forces Institute of Pathology with ambiguous genitalia and hyperpigmentation. He had family history of CAH. His laboratory investigations revealed normal serum cortisol and 17 Hydroxy (17 OH) progesterone levels with high plasma ACTH and renin levels. He had low aldosterone with inadequate response with hCG stimulation test. This is the first case of non-classic LCAH reported in the Pakistani population. Steroidogenic acute regulatory protein (StAR) gene mutations result in LCAH and the condition should be considered in the differential diagnosis of an XY child with primary adrenal insufficiency.

Evaluation of multiple risk factors involved in the development of Diabetic Retinopathy.

OBJECTIVE: To determine the role of hypertension, hyperlipidemia, smoking and positive family history of diabetes and hypertension in the development of diabetic retinopathy. METHODS: This prospective cohort study was conducted at the Department of Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi over 2 years period from June 2014 to June 2016. One hundred consecutive diabetic patients with no signs of diabetic retinopathy and good glycemic control (HbA1c<6.5%) were registered by non-probability convenient sampling after taking written informed consent. They were evaluated for hypertension, hyperlipidemia and smoking status. These patients were then followed 6 monthly for 2 years to look for the development of diabetic retinopathy. RESULTS: The mean age of the patients was 50.72±9.29 years and there were 57 (57%) male and 43 (43%) female patients. Majority (82%) of the patients had NIDDM. The mean duration of diabetes was 8.31±6.83 years. 11% of the patients were smoker, 37% were hypertensive, 6% had hyperlipidaemia, 62% had family history of diabetes and 30% had family history of hypertension. At the end of follow-up, 9 (9.0%) patients had diabetic retinopathy. The frequency of diabetic retinopathy increased with increasing age of the patient; however, the difference was statistically insignificant. A comparatively higher frequency of diabetic retinopathy was also seen in patients with IDDM and those with positive family history of diabetes and hypertension yet again, the difference was statistically insignificant. Also, no significant difference was noted among male and female genders and smokers vs. non-smoker. However, the frequency of diabetic retinopathy increased significantly with increasing duration of diabetes. It was also higher among those with hypertension and hyperlipidemia. CONCLUSION: Higher patient age (≥50 years), increasing duration of diabetes (≥20 years), insulin dependent diabetes mellitus, hypertension, hyperlipidemia, and positive family history of diabetes and hypertension were found to be associated with increased frequency of diabetic retinopathy.

Frequency of Primary Hyperaldosteronism in Young Hypertensives in a Tertiary Care Setting of Rawalpindi.

OBJECTIVE: To determine the frequency of primary hyperaldosteronism in young hypertensives in hospital settings of Rawalpindi. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology (AFIP), Rawalpindi, from June 2016 to May 2017. METHODOLOGY: Two hundred and fifty patients with hypertension (blood pressure of more than 140/90 mm Hg) of both genders, with age between 17-40 years were recruited in the study. Patients on anti-hypertensive medications, renal function derangement, pregnant females and those labelled with secondary hypertension were excluded. Blood samples were taken for the analyses of plasma renin, aldosterone, electrolytes, and blood gases. Parametric quantitative variables were presented as mean + SD. RESULTS: Eight cases, out of a total 80 subjects fulfilling the inclusion criteria, were diagnosed with primary hyperaldosteronism and 72 with essential hypertension. Mean age of patients having primary hyperaldosteronism was 29.25 +7.1 years. The mean diastolic blood pressure of all patients was 90.3 +6.5 mm of Hg, while mean systolic blood pressure was 142.7 +10.5 mm of Hg. CONCLUSION: Frequency of primary hyperaldosteronism was found to be 10%, emphasising on the fact that it is not very uncommon in young hypertensives.

Determination of reference intervals of thyroid markers during pregnancy in Urban area of District Rawalpindi Pakistan.

OBJECTIVE: To determine the reference values for thyroid stimulating hormone, free tetra-iodothyronine and total tri-iodothyronine for healthy pregnant women. METHODS: This cross sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January 2016 to June 2017. Pregnant women with normal, single intrauterine, uncomplicated pregnancy were recruited from the local population. Blood sample was taken to analyse thyroid stimulating hormone, free tetra-iodothyronine and total tri-iodothyronine using chemiluminescence immunoassay. For thyroid hormone levels during each trimester 5th and 95th percentiles were calculated as reference intervals. Data was analysed using SPSS 24. RESULTS: Out of 384 subjects, 188(48.95%) were in their first trimester and 196(51.04 %) females were in their second trimester. There were 109(57.97%) primigravida in the first trimester and 137(69.9%) in the second trimester. Mean age of subjects presenting in the first and second trimester was 25.37±3.78 years and 26.54±4.65 years respectively. Reference intervals for those in the first trimester for thyroid stimulating hormone was 0.05-2.8uIU/ml, for free tetra-iodothyronine14.4-22.7pmol/l and total tri-iodothyronine1.5-3.3nmol/l. For those in second trimester the corresponding values were 0.16-3.3 uIU/ml, 14.2-24.6.0 pmol/l and 1.6-3.1nmol/l. CONCLUSIONS: Laboratories should adopt trimester-specific reference intervals for thyroid function tests in pregnancy..

Acrophobia in a Young Girl with Parathyroid Hormone Resistance (Pseudohypoparathyroidism).

Pseudohypoparathyroidism (PHP) is an extremely rare group of disorders. It is a spectrum of disorders caused by end organ resistance to parathyroid hormone (PTH) and is represented by impaired signalling that activates cAMP dependent pathways via alpha subunit of G-protein (GS). It is characterised by hypocalcemia, hyperphosphatemia, raised PTH levels due to insensitivity to biological activity of PTH, and normal renal function tests. We describe a case of 10-year girl who presented with fear of falling down from heights. Her laboratory evaluation and skeletal survey showed evidence of PHP along with features of Albright's hereditary osteodystrophy (AHO) pointing towards the diagnosis of PHP type 1a.

Spectrum of renin angiotensin aldosterone system disorders in young hypertensives.

OBJECTIVE: To analyse the spectrum of renin angiotensin aldosterone system disorders in young hypertensive patients in hospital settings. METHODS: This cross-sectional study was conducted at the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from January to December, 2016. It comprised hypertensive subjects aged 17-40 years of either gender presenting in the outpatient department. All subjects were having blood pressure more than 140/90mmHg and were not on any anti-hypertensive medicine. Blood sample was taken from each patient to analyse arterial blood gases, plasma renin, serum aldosterone and electrolytes. Association of qualitative variables like age, systolic and diastolic blood pressure with essential hypertension and primary hyperaldosteronism was explored. RESULTS: Of the 80 patients, 72(90%) were diagnosed with essential hypertension and 8(10%) with primary hyperaldosteronism. None of the patients had Liddle syndrome, apparent mineralocorticoid excess or Gordon syndrome. Mean age of patients having essential hypertension was 30.97±7.1 years, whereas, for those with primary hyperaldosteronism it was 29.25±7.1 years. Systolic blood pressure was significantly higher (p = 0.000) among all patients. No statistically significant association was found between age, systolic and diastolic blood pressure (p<0.05). CONCLUSIONS: Primary hyperaldosteronism as compared to other renin angiotensin aldosterone system disorders was found to be the leading cause of hypertension in young population.

Cost-effectiveness of Screening and Confirmatory Tests for Multiple Myeloma in Pakistani Population: An Audit Report.

OBJECTIVE: To find out the use of screening and confirmatory tests for diagnosis of multiple myeloma as ordered by clinicians. STUDY DESIGN: An Audit. PLACE AND DURATION OF STUDY: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from January 2012 to January 2017. METHODOLOGY: Data retrieved from Laboratory Information Management system (LIMs) by selecting serum protein electrophoresis (SPE) as screening test and immunoelectophoresis (IE) and immunofixation (IF) as confirmatory tests. RESULTS: There were 3,108 tests of serum protein electrophoesis and 1,329 tests of immunoelectophoresis had been performed in last five year. Cost-effective clinical audit of SPE tests showed that only 17.1% tests of SPE were either used for proper diagnosis of multiple myeloma (totally justified tests 13%) or useful for diagnosis of other important diseases whose early diagnosis were helpful for patients management (partially justified tests 4.1%). The cost related to these tests were justified while 82.8% tests of SPE were either normal (total unjustified tests 24.4%), or diagnosed irrevalent and nonspecific diseases (partially unjustified 58.4%). IE and IF audit revealed that only 26.6% tests were properly utilised for diagnosis and differentiation of multiple myeloma and its subtypes and cost attributable to these tests were justified while 73.4% of these confirmatory tests were normal and cost related to them was not justified. CONCLUSION: Overutilisation of laboratory tests for diagnosis of multiple myeloma can be minimised by proper clinical scrutiny of request forms.