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Familial hCG syndrome is a rare and benign cause of elevated serum beta human chorionic gonadotropin (hCG). We present here a case of familial hCG syndrome diagnosed in a Hong Kong Chinese family, which we believe to be the first reported in Chinese. A 38-year-old woman presented with incidental finding of persistently elevated hCG, analytically confirmed both in urine and blood. Extensive radiological and biochemical work-up were performed but were negative for pregnancy and malignancy. Testing of another asymptomatic family member revealed unexplained elevation of serum hCG, confirming the diagnosis of familial hCG syndrome. Knowledge and awareness of this entity among clinicians are important to avoid unnecessary investigations and treatment in affected families.

Isolated 17,20-lyase deficiency may be caused by mutations in the CYP17A1 (coding for cytochrome P450c17), POR (coding for cytochrome P450 oxidoreductase) and CYB5A (coding for microsomal cytochrome b5) genes. Of these, mutations in the CYB5A gene have thus far only been described in genetic males who presented with methemoglobinemia and 46,XY disorders of sex development (DSD) due to 17,20-lyase deficiency. A 24-year-old Chinese woman presented to the hematology outpatient clinic with purplish discoloration of fingers, toes, and lips since childhood. Investigations confirmed methemoglobinemia. A homozygous c.105C>G (p.Tyr35Ter) nonsense mutation was detected in the CYB5A gene. Hormonal studies showed isolated 17,20-lyase deficiency. Interestingly, she had a completely normal female phenotype with no DSD, normal pubertal development, and spontaneous pregnancy giving birth uneventfully to a healthy female infant. The sex hormone-related features of genetic females with 17,20-lyase deficiency due to cytochrome b5 gene mutation appear to differ from that of females with 17,20-lyase deficiency caused by other genetic defects who presented with hypergonadotropic hypogonadism and infertility and differ from genetic males with the same mutation.

Introduction Newborn screening is important for early diagnosis and effective treatment of inborn errors of metabolism (IEM). In response to a 2008 coroners' report of a 14-year-old boy who died of an undiagnosed IEM, the OPathPaed service model was proposed. In the present study, we investigated the feasibility of the OPathPaed model for delivering expanded newborn screening in Hong Kong. In addition, health care professionals were surveyed on their knowledge and opinions of newborn screening for IEM. Methods The present prospective study involving three regional hospitals was conducted in phases, from 1 October 2012 to 31 August 2014. The 10 steps of the OPathPaed model were evaluated: parental education, consent, sampling, sample dispatch, dried blood spot preparation and testing, reporting, recall and counselling, confirmation test, treatment and monitoring, and cost-benefit analysis. A fully automated online extraction system for dried blood spot analysis was also evaluated. A questionnaire was distributed to 430 health care professionals by convenience sampling. Results In total, 2440 neonates were recruited for newborn screening; no true-positive cases were found. Completed questionnaires were received from 210 respondents. Health care professionals supported implementation of an expanded newborn screening for IEM. In addition, there is a substantial need of more education for health care professionals. The majority of respondents supported implementing the expanded newborn screening for IEM immediately or within 3 years. Conclusion The feasibility of OPathPaed model has been confirmed. It is significant and timely that when this pilot study was completed, a government-led initiative to study the feasibility of newborn screening for IEM in the public health care system on a larger scale was announced in the Hong Kong Special Administrative Region Chief Executive Policy Address of 2015.

Introduction There is a pressing need to identify diagnostic testing for Cushing's syndrome that can be achieved with ease and at low cost. This study aimed to explore the usefulness of late-night and post-overnight 1-mg dexamethasone suppression salivary cortisone, as measured by liquid chromatography-tandem mass spectrometry, for investigation of hypercortisolism. Methods Salivary cortisone data of subjects were investigated according to a pre-specified protocol. Subjects were classified as having 'hypercortisolism' or 'eucortisolism' on the basis of histological or biochemical criteria. Receiver operating characteristic curves were drawn to identify the cut-off values and study their performance characteristics. We measured 24-hour urinary free cortisol; late-night salivary cortisol and cortisone; and post-overnight 1-mg dexamethasone suppression serum cortisol, and salivary cortisol and cortisone. Saliva and urine samples were assayed by liquid chromatography-tandem mass spectrometry. Results In this study, 21 subjects were classified as having hypercortisolism and 78 as having eucortisolism. A late-night salivary cortisone cut-off of 13.50 nmol/L had a sensitivity of 94.7% and a specificity of 87.2%. After taking 1-mg dexamethasone the night before, a salivary cortisol cut-off of 0.85 nmol/L had a sensitivity of 76.2% and a specificity of 96.2%; a salivary cortisone cut-off of 7.45 nmol/L had a sensitivity of 85.7% and a specificity of 94.9%, while a salivary cortisone cut-off of 3.25 nmol/L had a sensitivity of 95.2% and a specificity of 79.5%. Many salivary cortisol samples were below the detection limit of liquid chromatography-tandem mass spectrometry. In comparison with salivary cortisol, salivary cortisone had a better correlation with total serum cortisol and better diagnostic performance following dexamethasone suppression. Conclusions Both late-night and post-overnight dexamethasone suppression salivary cortisone levels are of diagnostic value in the investigation of hypercortisolism.

Aim: Setting up reference intervals from the local service populations is one of the major responsibilities of clinical laboratories. Yet, this task is difficult to achieve because it is costly and time consuming when compared with validating reference intervals from assay manufacturers. Methods: Following the recommendations of the International Federation of Clinical Chemistry, healthy local Chinese adults were recruited to set up reference intervals for common serum analytes. Statistical methods recommended by the National Committee for Clinical Laboratory Standards were used for defining the reference limits. Results: Data from 335 subjects were analysed. The reference intervals set up were broadly similar to those provided by the assay manufacturer, except for sodium and potassium. Glomerular filtration rate was estimated by the modification of diet in renal disease equation, with or without modification for Chinese. Body mass index had a significant impact on serum urate and alanine aminotransferase levels. Conclusion: Reference intervals of common serum analytes have been set up for the local Chinese population. A good example of quality laboratory service has also been set up to provide clinicians with reliable reference intervals that they can confidently rely on for the diagnosis and management of patients.

Recent reviews recommended the use of the aldosterone/renin ratio (ARR) to screen for primary hyperaldosteronism. However, widely different cutoff levels have been proposed, and test characteristics of ARR under different conditions of sampling are not known. We conducted a retrospective review among 45 subjects with carefully validated diagnoses of primary hyperaldosteronism and 17 subjects with essential hypertension to study the utility of ARR. Sixty-two patients with 75 sets of plasma renin activity (PRA), aldosterone, and ARR values from a postural study and 48 sets of values from a saline suppression test were analyzed. Ninety-four percent of these subjects underwent investigations because of hypokalemic hypertension.ARR yielded larger areas under the curve in the receiver-operating-characteristics curve than PRA or aldosterone under all conditions of testing. Our results confirmed the superiority of ARR to either aldosterone or PRA alone as a diagnostic test for primary hyperaldosteronism.ARR cutoff levels were significantly affected by the condition of testing. Depending on posture and time of day, it varied from 13.1-35.0 ng/dl per ng/ml.h in our study population. When using ARR for screening primary hyperaldosteronism, posture and time of sampling should be standardized both within and between centers to minimize variability in cutoff levels.

During the seven years from January 1989 to December 1995, we investigated 2,269 Chinese infants and young children for metabolic disorders in Hong Kong. These young patients, all aged under 4 years and originated from southern China, were ill with no apparent cause and had clinical manifestations suggestive of inherited metabolic diseases. A spot urine and a plasma sample were obtained from each patient for biochemical analysis, including urinary organic acid identification and plasma amino acid analysis. Six cases of mucopolysaccharidosis, four multiple carboxylase deficiency, three 2-methylacetoacetyl CoA thiolase deficiency, two methymalonic aciduria, one glutaric aciduria type I, one glutaric aciduria type II, one a-oxoglutaric aciduria, and one case of orotic aciduria were detected. There were also single suspected cases of medium-chain acyl-CoA dehydrogenase deficiency and isovaleric aciduria. No primary amino acid disorder, such as phenylketouria and maple syrup urine disease, has been detected. Our results suggest that a different pattern of inherited metabolic diseases exists in the southern Chinese when compared with the Chinese in other regions of China.

BACKGROUND 5α-Reductase 2 deficiency (5ARD) is a known cause of 46,XY disorders of sex development (DSD). Traditionally, the diagnosis relies on dihydrotestosterone (DHT) measurement, but the results are often equivocal, potentially leading to misdiagnosis. We reviewed alternative approaches for diagnosis of 5ARD. METHODS We conducted a retrospective review of the results of urinary steroid profiling (USP) by GC-MS and mutational analysis of SRD5A2 [steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2)] by PCR and direct DNA sequencing of all 46,XY DSD patients referred to our laboratory with biochemical and/or genetic findings compatible with 5ARD. We also performed a literature review on the laboratory findings of all 5ARD cases reported in the past 10 years. RESULTS Of 16 patients diagnosed with 5ARD between January 2003 and July 2012, 15 underwent USP, and all showed characteristically low 5α- to 5β-reduced steroid metabolite ratios. Four patients had DHT measured, but 2 did not reach the diagnostic cutoff. In all 12 patients who underwent genetic analysis, 2 mutations of the SRD5A2 gene were detected to confirm the diagnosis. Twenty-four publications involving 149 patients with 5ARD were published in the review period. Fewer than half of these patients had DHT tested. Nearly 95% of them had the diagnosis confirmed genetically. CONCLUSIONS 5ARD can be confidently diagnosed by USP at 3 months postnatally and confirmed by mutational analysis of SRD5A2. Interpretation of DHT results may be problematic and is not essential in the diagnosis of 5ARD. We propose new diagnostic algorithms for 46,XY DSD.

Severe acute respiratory syndrome (SARS) is a contagious viral disease caused by a novel coronavirus (SARSCoV) and transmitted through droplets and close contact [1]. Healthcare workers (HCWs) are particularly at risk when looking after SARS patients. As reported by the World Health Organization [2] more than 20% (386) of those infected with SARS in Hong Kong were HCWs. Described here are the infection control procedures undertaken at a hospital in Hong Kong when three Caesarean sections were performed on women with active maternal SARS infection. SARS-CoV infection had been confirmed by reverse transcriptase polymerase chain reaction in all three mothers prior to the time of operation. The operations were performed between 1 April and 5 April 2003. None of the HCWs (>15) involved in the three separate operations developed fever or clinical SARS within 14 days of exposure. When the operations were performed, the Centers for Disease Control and Prevention (CDC; Atlanta, Ga., USA) had not yet prepared guidelines for the prevention of SARS transmission during Caesarean sections. Since these procedures are associated with the use of suction irrigation and diathermy, it was likely that body fluid and blood would spill and evaporate into the room during the operation. Therefore, the procedures were assumed to be aerosol generating, and previously described precautions to prevent contact and airborne infection were undertaken to prevent nosocomial SARS infection [3]. Although the CDC provided guidelines for the prevention and control of SARS infection on 6 May 2003 [4], those guidelines have, to the best of our knowledge, never been tested for the procedure described here. Following are the steps and procedures we undertook to prevent HCWs in our hospital from contracting SARS. For the three Caesarean sections performed on mothers with SARS, the number of healthcare workers was limited to a minimum, with only those personnel essential to carry out the operation, neonatal resuscitation, and cleanup being involved (i.e., 2 senior obstetricians, 2 senior neonatologists, 1 senior anaesthetist, 1 theatre assistant, a team of 4 senior midwives, and 2 cleansing staff). A nurse supervisor was designated as in-charge and was responsible for monitoring the other HCWs with regard to the use of personal protective equipment (PPE), cleansing of the room, sterilising the equipment and transferring the patients. She ensured all HCWs had fit-tested their respirators. She was also responsible for testing the portable high-efficiency particulate air filter (HEPA) units (Air-Mate PAPR; USA), checking the batteries, and training other HCWs on the proper use of the HEPA units. All unnecessary instruments were removed from the operating theatre. Extra laparotomy instruments were prepared to deal with possible intra-operative complications. Two bags of blood were made available in the theatre for the operation. Disposable instruments were used if available. To avoid spillage of blood, drapes with plastic bags on the sides were used. An operating theatre separate from the main theatre block was designated for this type of surgery in order to minimise contamination of the main theatre. The door of the operating theatre was kept closed during the operation, except when participating personnel entered or left the room. In order to keep the number of entrances and exits to a minimum during the operation, most of the equipment was prepared before the patient arrived. The air circulation was adjusted to 20 exchanges per minute. Negative pressure was created within the operating theatre relative to the adjacent room or hallway; thus, S. F. Wong ()) · K. M. Chow · Y. P. Leung · A. Chiu · P. W. Y. Lam · L. C. Ho Department of Obstetrics and Gynaecology, Maternal Fetal Medicine Unit, Princess Margaret Hospital, Lai Chi Kok, Kowloon, Hong Kong e-mail: shellwong@hotmail.com Tel.: +1-852-29901111 Fax: +1-852-29903488

An 8-year-old asymptomatic child was genetically diagnosed to have resistance to thyroid hormone (RTH) during a family screening. The disease-causing mutation is inherited from his father. Retrospective study showed the boy had a normal umbilical cord blood thyrotropin (TSH) level, suggesting that umbilical cord blood TSH may not reflect the fetal pituitary-thyroid axis abnormality and prenatal diagnosis and treatment should not be recommended in patients with mild RTH phenotype.

SUMMARY objective To study the age-related changes in bone density, serum parathyroid hormone, calcium absorption and other indices of calcium metabolism in Chinese women who habitually have a low calcium intake design Cross-sectional study subjects One hundred and fifty-six healthy Chinese women aged 20–83 years. None were on any medication or vitamin supplements. Subjects over the age of 60 years were all living in a hostel; younger subjects were nurses or subjects attending a family clinic for minor illnesses measurements Fasting blood and urine samples were collected for biochemical measurements and calcium absorption was measured using Ca by the method of Marshall and Nordin. Bone density was measured by dual energy X-ray densitometry (Norland X R20 X-ray bone densitometer) at the left hip and lumbar spine. Serum parathyroid hormone was measured by a chemiluminometric assay results Plasma Ionized calcium concentration, alkaline phosphatase, bicarbonate, plasma creatinine and serum B2 microgiobulin were significantly higher in the elderly than in the young, whereas plasma phosphate and the anion gap were higher in the young. Urinary excretion of calcium, phosphate and hydroxyproiine were all higher in older women. Plasma parathyroid hormone concentration was positively correlated with age even after taking into account the decline in renal function (as indicated by the rise in B2 microglobulin (r= 0·506, P > 0·001). Serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were not lower In the older women. Fractional calcium absorption from an oral load of radlolabelled calcium was slgnificantly lower in the older women and 37% of the older women were below the 2.5 percentile found in the younger women. Bone density measured by dual energy X-ray densitometry was also significantly lower in the elderly. conclusion In Chinese women there is an Increase in PTH and a decrease in calcium absorption with age in spite of the presence of normal vitamin D metabolites

To evaluate the relation between chorioamnionitis and hypotension in very low birthweight infants.Retrospective cohort study in infants with a birth weight of1500 g born between January 2002 and September 2004. The placentas were examined for evidence of chorioamnionitis and funisitis. Hypotension was defined by the use of vasopressors.Of 105 infants, 37 (35%) were chorioamnionitis positive. The onset of hypotension had a skewed distribution: day 1 for 30 episodes and scattered from day 2 to day 19 for the remaining 22. Of the 30 infants who developed hypotension on day 1, 17 (57%) were chorioamnionitis positive. The mean maturity of the chorioamnionitis positive group was 27.91 weeks, marginally less than the mean maturity of 29.05 weeks of the chorioamnionitis negative group (p = 0.05). After adjustment of the effects for confounding variables (birth weight, gestation, surfactant therapy, mechanical ventilation on day 1, high frequency oscillatory ventilation, patent ductus arteriosus), chorioamnionitis was the significant factor in line with hypotension developing on day 1 (adjusted odds ratio 5.14, 95% confidence interval 1.51 to 17.50). There was no evidence that hypotension developing after day 1 was associated with chorioamnionitis.There is a strong association between chorioamnionitis and hypotension developing on day 1 in very low birthweight infants.

We report on the first Chinese patient with triple-A syndrome, who presented at 22 months with status epilepticus secondary to hyponatraemia and hypoglycaemia. Subsequent endocrine investigations confirmed primary adrenal insufficiency and aldosterone deficiency. In the presence of achalasia and alacrima, this patient satisfies the diagnostic criteria of triple-A syndrome. Further molecular testing detected compound heterozygous mutations in the AAAS gene: a c.580C --> T transition in exon 7 and a c.771delG single nucleotide deletion in exon 8. Testing of parents and brother confirmed their heterozygous carrier status.

Bone mineral density (BMD) has been shown to be increased in postmenopausal females with postthyroidectomy hypoparathyroidism, but it is not known whether similar gains occur in patients with idiopathic hypoparathyroidism. In this study, we measured the BMD of lumbar spine and proximal femur in 14 patients, 8 with idiopathic hypoparathyroidism and 6 with postthyroidectomy hypoparathyroidism, using dual-energy x-ray absorptiometry. Their age ranged from 23-57 yr old, with a mean of 42.5 yr. The results showed that patients with hypoparathyroidism had a higher BMD than the normal age- and sex-matched population. This was particularly evident at the lumbar spine (L2-L4), with positive Z-score of 1.93 +/- 1.03, whereas Z-score at the femoral neck was 1.14 +/- 0.62 SD. Subgroup analysis showed that those with postthyroidectomy hypoparathyroidism had a mean lumbar spine BMD of 1.434 g/cm(2) and femoral neck BMD of 1.026 g/cm(2), compared with a mean BMD of 1.364 g/cm(2) and 1.022 g/cm(2) at spine and hip, respectively, for those with idiopathic hypoparathyroidism. Statistical analysis did not reveal any significant difference in the BMD, T-score, and Z-score of the bone, at these two sites, between the two groups. In conclusion, the state of chronic hypoparathyroidism is associated with increased BMD, especially at the lumbar spine. Those with idiopathic hypoparathyroidism have a similar degree of increase in BMD as those with postthyroidectomy hypoparathyroidism.

Summary We report a case of congenital adrenal hyperplasia due to 17 α-hydroxylase deficiency in a Chinese genotypic male patient. Despite the male genotype, normal female external genitalia were present and with the introduction of cyclical oestrogen therapy withdrawal bleeding occurred, confirming the presence of functional endometrial tissue. We believe this to be the first report of persistent Mullerian duct structures in a genotypic male with 17 alpha-hydroxylase deficiency. It could be explained by either impaired secretion or impaired action of anti-Mullerian hormone. Further, contrary to the usual finding of suppressed aldosterone secretion, this patient had measurable levels of plasma aldosterone.

SUMMARY objective To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH-like activity in patients with primary hepatocellular carcinoma design After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various anaytes and results compared between various groups patients Fifty-five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only measurements Serum calcium, phosphate, aikaline phosphatase, albumin, creatinine and urinary calcium, creatnine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Dioagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods results Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P > 0·05) phosphate, PTH and TmP/GFR and elevated NcAMP (P > 0·001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P > 0·001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercaicaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH. conclusion We conciude that a PTH-like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed

Disorders of sex development (DSD) are defined as congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. In 46, XY DSD, the genotype is XY, but the external genitalia is incompletely virilised, ambiguous, or completely female. The objectives of this prospective study are to evaluate the testicular Sertoli and Leydig cell functions, to establish the genetic basis and to determine the relative prevalence of etiologies in Chinese patients with 46,XY DSD in Hong Kong. All patients with 46,XY DSD (either new or known) presented to five paediatric departments in Hong Kong from July 2009 till June 2011 were recruited. They were assessed by paediatric endocrinologists. Comprehensive evaluation of testicular and adrenal functions was performed using serum hormonal assays and urine steroid profiling. Based on the hormonal results, mutational analyses of the candidate genes by polymerase chain reaction and direct DNA sequencing were conducted to delineate the genetic basis of the etiologies. Sixty-five patients (54 male and 11 female) with 46,XY DSD were recruited. Their age ranged from birth to 27 years. Sixty-one (94%) patients presented with ambiguous external genitalia, two presented with delayed puberty and one each with primary amenorrhoea and inguinal hernia. Definitive diagnoses were made in 25 (38%) patients. Eleven (17%) patients had 5-alpha reductase 2 deficiency. Androgen insensitivity was confirmed by genetic analysis in eight (12%) patients. There was one patient with each of the following etiologies: Swyer syndrome, SF-1 mutation, Frasier syndrome, cholesterol side-chain cleavage deficiency, persistent Mullerian duct syndrome and mixed gonadal dysgenesis. Genetic basis of the etiologies was delineated in 23 (35%) patients. A total of 10 novel mutations were identified. The longest follow up period was 27 years, none of the patients requested change of gender sex so far. In conclusion, 46,XY DSD is a heterogeneous group with diverse etiologies. Although 5-alpha reductase 2 deficiency is believed to be rare, it is not uncommon in Hong Kong.