Primitive neuroectodermal adrenal gland tumour.

Ewing's sarcoma, also called primitive neuroectodermal tumour of the adrenal gland, is extremely rare. Only a few cases have been reported in the literature. We report on a woman with adult-onset primitive neuroectodermal tumour of the adrenal gland presenting with progressive flank pain. Computed tomography confirmed an adrenal tumour with invasion of the left diaphragm and kidney. Radical surgery was performed and the pain completely resolved; histology confirmed the presence of primitive neuroectodermal tumour, for which she was given chemotherapy. The clinical presentation of this condition is non-specific, and a definitive diagnosis is based on a combination of histology, as well as immunohistochemical and cytogenic analysis. According to the literature, these tumours demonstrate rapid growth and aggressive behaviour but there are no well-established guidelines or treatment strategies. Nevertheless, surgery remains the mainstay of local disease control; curative surgery can be performed in most patients. Adjuvant chemoirradiation has been advocated yet no consensus is available. The prognosis of patients with primitive neuroectodermal tumours remains poor.

Role of blood transfusion in trichosanthin-induced anaphylaxis.

Trichosanthin (TCS) is a type 1 ribosome inactivating protein extracted from Chinese medicinal herb. It possesses various biological functions such as abortifacient, anti-tumor and anti-viral activities. Clinical trial of this compound against human immunodeficiency virus (HIV) had been conducted. However, its use is limited by its high immunogenicity that elicits hypersensitivity reaction. This may lead to fatal anaphylactic response. The study described an approach of using blood transfusion to reduce TCS induced anaphylaxis in rats using a cross-circulation model. A TCS-sensitized Sprague Dawley rat was connected to a normal rat via the femoral vessels in a cross-circulation circuit before antigenic challenge. The donor rat served as a blood exchange basin to lower the level of the blood-borne components responsible for the anaphylactic reaction in the sensitized rat. Our results showed that cross-circulation shortened the duration of circulatory hypotension and reduced mortality of TCS induced anaphylaxis. The control group not undergoing cross-circulation had a mortality of 50% at 2h post-TCS challenge and there was no mortality in the cross-circulation group. This demonstrated that prior blood transfusion can be one of the alternatives to reduce anaphylactic response of TCS.

Increased high sensitivity C reactive protein concentrations and increased arterial stiffness in children with a history of Kawasaki disease.

OBJECTIVES: To test the hypothesis that low grade inflammation persists after the acute phase and affects arterial stiffness in children with a history of Kawasaki disease. DESIGN AND PATIENTS: A cohort of 106 children was studied, which comprised 43 patients with Kawasaki disease with coronary aneurysms (group I), 28 patients with Kawasaki disease with normal coronary arteries (group II), and 35 healthy age matched children (group III). Their systemic blood pressure, fasting cholesterol concentrations, serum high sensitivity C reactive protein (hs-CRP) concentrations, and carotid artery stiffness index were compared. Significant determinants of serum hs-CRP concentration and carotid artery stiffness were identified and the relation between hs-CRP concentration and arterial stiffness was investigated. SETTING: Tertiary paediatric cardiac centre. RESULTS: Serum hs-CRP concentration of group I patients (median 0.39 mg/l, interquartile range 0.28-0.65 mg/l) was significantly greater than that of group II (median 0.24 mg/l, interquartile range 0.17-0.29 mg/l, p < 0.001) and of group III patients (median 0.25 mg/l, interquartile range 0.18-0.40 mg/l, p < 0.01). Likewise, carotid artery stiffness index of group I patients (mean (SD) 5.07 (1.11)) was significantly greater than that of group II (4.27 (0.83), p = 0.002), and of group III patients (4.24 (0.86), p = 0.001). For the entire cohort, the carotid artery stiffness index correlated positively with log serum hs-CRP concentration (r = 0.24, p = 0.013). In multiple linear regression analysis, age (standardised beta = 0.22, p = 0.02), systolic blood pressure (standardised beta = 0.28, p = 0.01), log serum hs-CRP concentration (standardised beta = 0.21, p = 0.017), and patient grouping (standardised beta = -0.36, p < 0.001) were all independently associated with the carotid artery stiffness index. CONCLUSIONS: These findings support the possibility of ongoing low grade inflammation late after the acute phase of Kawasaki disease in patients with coronary aneurysms. Furthermore, this low grade inflammation may have a role in increasing systemic arterial stiffness.

Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation.

Adiponectin may have an antiatherogenic effect by reducing endothelial activation. We hypothesized that plasma adiponectin levels were correlated with endothelial function. Plasma adiponectin level was determined by an in-house RIA assay using a rabbit polyclonal antibody in 73 type 2 diabetic patients and 73 controls. Endothelium-dependent and independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. Plasma adiponectin level was lower in diabetic patients than in controls (4.73 +/- 1.96 vs. 7.69 +/- 2.80 microg/ml, respectively; P < 0.001), and they also had impaired endothelium-dependent (5.6 +/- 3.6 vs. 8.6 +/- 4.5%, respectively; P < 0.001) and -independent vasodilation (13.3 +/- 4.9 vs. 16.5 +/- 5.6%, respectively; P < 0.001). Plasma adiponectin correlated with endothelium-dependent vasodilation in controls (P = 0.02) and diabetic patients (P = 0.04). On general linear-model univariate analysis, brachial artery diameter, the presence of diabetes, plasma adiponectin, and high-density lipoprotein were significant independent determinants of endothelium-dependent vasodilation. In vitro experiments showed that endothelial cells expressed adiponectin receptors, and adiponectin increased nitric oxide production in human aortic endothelial cells. In conclusion, low plasma adiponectin level is associated with impaired endothelium-dependent vasodilation, and the association is independent of diabetes mellitus. Adiponectin may act as a link between adipose tissue and the vasculature.

Sitosterolaemia and xanthomatosis in a child.

A 4-year-old boy presented with multiple tuberous xanthomata and a fasting plasma sterol concentration of 18.3 mmol/L, consisting primarily of cholesterol. Two months after changing from an unrestricted diet to a cholesterol-lowering diet, the plasma sterol concentration decreased to 4 mmol/L. Fasting plasma cholesterol levels for his father and mother were 7.3 mmol/L and 6.0 mmol/L, respectively. The degree and rapidity of the child's response to dietary control, together with the fasting cholesterol results of both parents suggested a diagnosis of sitosterolaemia. Gas chromatography and mass spectrometry of the patient's plasma sterol levels showed that the percentage of beta-sitosterol was raised at 12.76%, as was campesterol (6.26%), and stigmasterol (0.71%), confirming the diagnosis of sitosterolaemia. The addition of cholestyramine 4 g/day to a low sterol diet maintained the plasma sterol concentration at 4 to 5 mmol/L, and gradual regression of the xanthoma was observed. These findings indicate that a diagnosis of sitosterolaemia, a treatable cause of premature atherosclerosis, should be considered in children with severe hypercholesterolaemia whose plasma cholesterol level is highly responsive to dietary manipulation.

Genetics of familial amyloidotic polyneuropathy in a Hong Kong Chinese kindred.

Familial amyloidotic polyneuropathy type 1 (FAP1, MIM176300) is an autosomal dominant disease caused by mutations in the transthyretin (TTR) gene. An extended Chinese kindred of FAP1 was first reported in Hong Kong in 1989, three of the four histologically proven subjects have deceased. TTR gene mutations were not studied then. A DNA-based diagnosis was performed on FAP1 by restriction analysis and direct DNA sequencing was carried out on a symptomatic member of this family who had undergone a liver transplantation. It showed a substitution of thymine by cytosine in the second base of codon 30 in exon 2 of the TTR gene, with the creation of a novel HhaI restriction endonuclease site. Valine is substituted by alanine (V30A) in the mutant TTR. Both restriction analysis and direct sequencing revealed the same mutation in one of the two asymptomatic siblings. This mutation was first reported in a FAP1 family of German descent.

Acute effect of orlistat on post-prandial lipaemia and free fatty acids in overweight patients with Type 2 diabetes mellitus.

AIMS: Post-prandial lipaemia is prolonged and exaggerated in patients with Type 2 diabetes mellitus, with an accumulation of atherogenic triglyceride-rich lipoprotein remnants. We postulate that orlistat, a gastrointestinal lipase inhibitor, may cause changes in post-prandial lipoprotein metabolism by reducing dietary triglyceride absorption. METHODS: The acute effect of a single dose of 120 mg orlistat on post-prandial glucose, lipids, remnant lipoproteins and free fatty acids (FFA) was evaluated in a randomized, double-blind, placebo-controlled cross-over study of 63 overweight patients with Type 2 diabetes mellitus (body mass index 30.4 +/- 3.8 kg/m2). Either a single dose of orlistat or placebo was given before a standard mixed meal containing 70 g of fat and plasma triglyceride (TG), remnant-like particles cholesterol (RLP-C) and FFA were sampled at 2-h intervals for 8 h. RLP-C was measured by an immunoseparation assay and FFA by an enzymatic colorimetric method. RESULTS: The concentrations of plasma TG (P < 0.0001), RLP-C (P = 0.003), and FFA (P < 0.0001) were significantly lower at 2 h after orlistat compared with placebo. Both plasma RLP-C (P = 0.04) and FFA (P < 0.0001) remained lower after orlistat than placebo at 4 h. The incremental area under the curve (iAUC) above baseline fasting level for both TG and RLP-C was significantly more reduced after orlistat than placebo (iAUC-TG 5.8 (3.7-8.2) mmol/l x h-1 vs. 5.7 (4.1-10.9), respectively, P = 0.04; iAUC-RLP-C: 0.53 (0.23-1.04) mmol/l x h-1 vs. 0.56 (0.35-1.40), respectively, P = 0.02). The test meal was well tolerated by all subjects, with only three subjects reporting faecal urgency after orlistat. CONCLUSIONS: Orlistat has a beneficial effect on post-prandial lipaemia in overweight Type 2 diabetic patients and lowers plasma TG, RLP-C and FFA in the early post-prandial period.

The effect of pregnancy on thyroid nodule formation.

Epidemiology data have revealed a higher prevalence of nodular goiters in women than men in both iodine-sufficient and iodine-deficient areas. Increased prevalence of thyroid nodules has also been reported in women with higher gravidity. However, the association between pregnancy and thyroid nodule formation has never been studied. The aim of our study was to evaluate the incidence of thyroid nodules during pregnancy and determine whether pregnancy will induce thyroid nodule formation. Two hundred twenty-one healthy southern Chinese women in the first trimester of their pregnancy were studied prospectively. Thyroid ultrasonography, thyroid function tests, and urinary iodine excretion were measured at first, second, and third trimesters of pregnancy as well as 6 wk and 3 months postpartum. Thyroid nodules (>2 mm in any dimension on ultrasonography) were detected in 34 (15.3%) subjects at first trimester, with 12 (5.4%) subjects having more than one nodule. Eight subjects had clinically palpable nodules. Women with thyroid nodules were older (P < 0.01) and had higher gravidity (P < 0.02) than those women without thyroid nodules. The volume of the single/dominant nodules increased from 60 (14--344) mm(3), median (interquartile range) at first trimester to 65 (26-472) mm(3) at third trimester (P < 0.02). These nodules remained enlarged at 103 (25-461) mm(3) 6 wk postpartum (P < 0.005) and 73 (22-344) mm(3) at 3 months postpartum (P < 0.05). Patients with thyroid nodules had lower serum TSH values (P < 0.03) and higher Tg levels (P < 0.05) throughout pregnancy. Appearance of new nodules was detected in 25 (11.3%) women as pregnancy advanced so that by 3 months postpartum, the incidence of thyroid nodular disease was 24.4% (P < 0.02 vs. first trimester). Compared with those with no detectable nodules throughout pregnancy, subjects with new nodule formation had higher urinary iodine excretion from second trimester onward (P all < 0.05). However, no difference could be detected in their TSH and Tg levels throughout pregnancy. Fine-needle aspiration on nodules greater than 5 mm in any dimension after delivery (n = 21) confirmed the majority having histological features consistent with nodular hyperplasia. No thyroid malignancy was detected. In conclusion, pregnancy is associated with an increase in the size of preexisting thyroid nodules as well as new thyroid nodule formation. This may predispose to multinodular goiter in later life.

Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus.

Endothelial dysfunction is frequently found in diabetic subjects. This study was performed to investigate whether atorvastatin therapy was able to reverse endothelial dysfunction in type 2 diabetes and, if so, whether the effect was due to its antiinflammatory action. Eighty patients (baseline low density lipoprotein, 4.37 +/- 0.71 mmol/liter) were randomized to atorvastatin (10 mg daily for 3 months, followed by 20 mg daily for 3 months) or placebo in a double blind study. Endothelial function was assessed by high resolution vascular ultrasound, and high sensitivity C-reactive protein (CRP) was assessed by immunoturbidimetric assay. Diabetic patients had higher CRP (P < 0.01) than matched nondiabetic controls, and both endothelium-dependent and independent vasodilation were impaired (P < 0.01). Atorvastatin (10 and 20 mg) lowered plasma cholesterol by 32.9% and 38.0%, triglyceride by 15.4% and 23.1%, and low density lipoprotein by 43.4% and 50.1%, respectively. At 6 months, plasma CRP decreased in the atorvastatin group compared with baseline (P < 0.05). Endothelium-dependent vasodilation improved in the atorvastatin group compared with the placebo group (P < 0.05). The percent change in endothelium-dependent vasodilation at 6 months correlated with the percent change in CRP (r = -0.44; P < 0.05), but not with changes in plasma lipids. In conclusion, treatment with atorvastatin in type 2 diabetes led to a significant improvement in endothelium-dependent vasodilation, which might be partly related to its anti-inflammatory effect.

Parathyroid autotransplantation during thyroidectomy: documentation of graft function.

HYPOTHESIS: Biochemical function of normal parathyroid tissue grafted during thyroidectomy can be documented. DESIGN: An intervention study in which devascularized or inadvertently removed parathyroid glands are reimplanted in forearm muscle pockets during thyroidectomy. Postoperative serum parathyroid hormone levels were evaluated by venous sampling from both forearms on postoperative days 1, 3, 14, 28, 56, and 84. SETTING: Tertiary care teaching hospital. PATIENTS: Seven patients undergoing thyroidectomy at risk for postoperative hypocalcemia. RESULTS: A 1.5-fold gradient of parathyroid hormone measurements between grafted and nongrafted arms was demonstrated in all patients on postoperative day 28. A maximal parathyroid hormone gradient was reached on day 56, and biochemical function persisted in 6 patients on day 84. CONCLUSIONS: Biochemical function of parathyroid glands reimplanted during thyroidectomy can be demonstrated objectively. The application of parathyroid autotransplantation may preserve parathyroid function for inadvertently removed or devascularized parathyroid glands during thyroid surgery.

Porphyria cutanea tarda and melioidosis.

Porphyria cutanea tarda is a metabolic disorder in the haem biosynthetic pathway. It includes a heterogeneous group of conditions, which may be inherited or, more commonly, acquired. Although porphyria cutanea tarda presents with cutaneous lesions only, it is often associated with systemic disease. A 64-year-old Chinese patient, who developed sporadic porphyria cutanea tarda 1 year after the diagnosis of pulmonary melioidosis, is discussed. The patient presented with a history of recurrent photosensitive vesicles, blisters, and skin fragility on the sun-exposed areas of both forearms and hands, 6 months after commencing doxycycline and amoxycillin. Both the histological and biochemical findings were characteristic of porphyria cutanea tarda. All the lesions subsided after cessation of these antibiotics. The patient was free of further lesions at follow-up 6 months later. The association seen in this case between porphyria cutanea tarda and melioidosis is unlikely to be coincidental, because these two diseases are both very rare in Hong Kong. In addition, the temporal relationship between the antibiotic therapy and the clinical course of skin lesions in this patient suggests that the drugs were a trigger factor, precipitating their appearance.

A randomized controlled trial of low-dose recombinant human growth hormone in the treatment of malnourished elderly medical patients.

High-dose recombinant human GH (rhGH) has been shown to improve the nutritional status of malnourished older adults. It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function. There is also no data on the outcome after a short course of rhGH treatment. The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients, its effect on physical functions, and the intermediate term outcome after a 4-week rhGH treatment. The study design was a randomized, placebo-controlled, double-blind trial conducted in a university teaching hospital. The patients were 19 medically stable malnourished elderly subjects. Intervention in the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body weight (BW) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian. In the placebo group, equal volumes of normal saline per kilogram BW were given 3 times weekly together with the dietary intervention. The baseline demographic, anthropometric, nutritional, and hematological variables, measures of physical function, and insulin-like growth factor I levels in both groups were comparable. Compared with the placebo group, the GH-treated group showed a more rapid gain in BW (after 3 weeks, +1.27 +/- 0.36 vs. -0.28 +/- 0.37 kg; P = 0.008), total lean body mass (change after 3 weeks by bio-impedance analysis, +1.45 +/- 0.36 vs. -0.37 +/- 0.48 kg; P = 0.009) and a faster improvement in 5-m walking time (decrease after 4 weeks, 23.79 +/- 9.41 vs. 0.45 +/- 4.62 sec; P = 0.047). The hemoglobin level rose more in the rhGH than the placebo groups (change at 8 weeks, +0.84 +/- 0.34 vs. -0.42 +/- 0.29 g/dL; P = 0.012). Serum albumin level also showed a greater delayed increase in the rhGH group than in the placebo group (change at 8 weeks, +5.1 +/- 0.8 vs. 1.6 +/- 1.2 g/dL; P = 0.023). There was no statistically significant difference for other nutritional variables. There was a greater rise in the mean serum insulin-like growth factor I level at 4 weeks in the GH than in the placebo groups (197 +/- 58 vs. 54 +/- 26 U/L; P = 0.034). The improvement in the rhGH group gradually diminished on follow-up and became statistically insignificant 8 weeks after stopping rhGH treatment. There were no GH-related adverse effects. Low-dose rhGH was an effective and safe adjuvant to dietary augmentation for stable malnourished elderly subjects. It led to a faster gain in total lean body mass, which was associated with greater improvement in walking speed when compared with dietary intervention alone. There were no apparent side effects.

Enhancement of the anti-herpetic effect of trichosanthin by acyclovir and interferon.

Trichosanthin (TCS) is a type I ribosome-inactivating protein that has a wide range of pharmacological activities. The present study investigated the effectiveness of TCS on herpes simplex virus (HSV-1). The anti-viral activity and toxicity of TCS on Vero cells were measured. Results showed that the ED(50), TD(50) and the therapeutic indices were 38.5, 416.5 and 10.9 microg/ml, respectively. Anti-viral activity of TCS was substantially potentiated when it was used in conjunction with other anti-viral agents. The ED(50) of TCS was reduced 125-fold by acyclovir at a concentration of 0.001 microg/ml, which was practically devoid of significant anti-viral activity. Similarly, the ED(50) of TCS was reduced 100-fold by interferon-alpha2a at a concentration of 100 IU/ml. In conclusion, TCS is effective against HSV-1 and other anti-viral agents such as acyclovir or interferon can potentiate its action substantially.

Mild iodine deficiency and thyroid disorders in Hong Kong.

OBJECTIVES: To review evidence of iodine deficiency and clinical thyroid disorders in Hong Kong. DATA SOURCES: Publications on local dietary iodine intake, the iodine content of local food items, and clinical thyroid problems in the Hong Kong population. DATA EXTRACTION: Data was extracted and evaluated independently by the authors. DATA SYNTHESIS: Iodine is an essential nutrient. Iodine deficiency can lead to goitre, hypothyroidism, mental deficiency, and impaired growth. It is now appreciated that determination of goitre incidence in children alone may grossly underestimate the problem of iodine deficiency in a population. In total, the evidence indicates that iodine deficiency exists in Hong Kong, leading to clinical problems of transient neonatal hypothyroidism, goitrogenesis, and thyroid disorders in pregnant women and neonates, as well as thyroid dysfunction in the elderly. CONCLUSION: A supplementation programme aimed at a relatively uniform iodine intake is recommended to avoid deficient or excessive iodine intake in subpopulations.

Value of intra-arterial calcium stimulated venous sampling for regionalization of pancreatic insulinomas.

BACKGROUND: Intra-arterial calcium stimulation with hepatic venous sampling (ASVS) for insulin gradients has been reported to be the most sensitive preoperative localizing technique for insulinomas. We reviewed our experience with ASVS to localize and guide the treatment of insulinomas over the past decade. METHODS: Eighteen patients who underwent ASVS before surgical exploration for insulinoma were studied. The accuracy of ASVS was compared with intraoperative findings and other localizing studies. RESULTS: There were no complications arising from the procedures. A more than 2-fold step-up in insulin level 30 to 60 seconds after injection to at least 1 feeding artery was observed in 16 patients. Fourteen of the 16 solitary tumors (87.5%) were correctly located; 100% (6/6 tumors) at the head and 80% (8/10 tumors) at the body/tail. The overall accuracy of this test was 89%, compared with 11%, 33%, 38%, and 63% of ultrasonography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, respectively. Six enucleations and 10 distal resections were performed, which included 2 laparoscopic procedures. The combination of intraoperative ultrasonography with preoperative ASVS identified all tumors. CONCLUSIONS: ASVS is the most accurate preoperative localization tool for the localization of insulinomas and, in combination with intraoperative ultrasonography, can enhance surgical success.

Aldose reductase-deficient mice develop nephrogenic diabetes insipidus.

Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various diseases associated with diabetes mellitus, such as cataract, retinopathy, neuropathy, and nephropathy. However, its physiological functions are not well understood. We developed mice deficient in this enzyme and found that they had no apparent developmental or reproductive abnormality except that they drank and urinated significantly more than their wild-type littermates. These ALR2-deficient mice exhibited a partially defective urine-concentrating ability, having a phenotype resembling that of nephrogenic diabetes insipidus.

The effect of 3 years of recombinant growth hormone therapy on glucose metabolism in short Chinese children with beta-thalassemia major.

Growth retardation and diabetes mellitus are common in children and adolescents with beta-thalassemia major despite hypertransfusion regimen and iron chelation therapy. The purpose of this study was to investigate the effects of growth hormone (GH) treatment on glucose metabolism in children with beta-thalassemia major. GH therapy for 3 years improved the height SD scores of eight short prepubertal Chinese children with beta-thalassemia major from -2.15 +/- 0.90 to -1.14 +/- 0.78 (paired t-test, p = 0.01) without excessive advancement in bone age (ABA/CA = 0.95 +/- 0.27). There was no deleterious effect on glucose metabolism with no change in fasting blood sugar, serum fructosamine, fasting and stimulated insulin to intravenous glucose infusion (sum of 1+3 min insulin, In 1+3'; incremental insulin 0-10 min area above fasting concentrations, deltaInAUC0-10'; ratio of incremental 0-10 min insulin area above fasting concentrations over glucose area above fasting concentrations, delta0-10'AUCIn/G; ratio of incremental 0-10 min insulin over peak glucose above basal 0-10 min, delta0-10'InAUC/deltaGPeak), and glucose disappearance coefficient (Kg). Short term GH therapy improves the height of children with beta-thalassemia major but the effect of treatment on final height still needs to be determined.

Engineering of a mini-trichosanthin that has lower antigenicity by deleting its C-terminal amino acid residues.

Trichosanthin is a ribosome-inactivating protein that possesses antitumor and antiviral activities. Clinical trials of trichosanthin on AIDS patients, however, elicit anaphylactic reactions. To reduce the antigenicity of trichosanthin as a drug while preserving its biological activity, the C-terminal domain (residues 203 to 247), which contains a putative antigenic site, was systemically deleted. We have found that the minimum length of trichosanthin that can fold into an active conformation is residue 1 to 240. The mini-trichosanthin (C7) generated by deleting the last seven C-terminal amino acid residues has 2.7-fold decrease in antigenicity, 10-fold reduction in in vitro ribosome-inactivation activity, and in vivo cytotoxicity toward K562 cells, and 2-fold reduction in abortificient activity. Structural analyses of C7 indicate decrease in the helix content, increased exposure of Trp192, and lower thermodynamic stability. The deletion of the C-terminal residues (Leu241 to Ala247) probably perturbs local structure of the C-terminal antigenic epitope that results in the decrease in antigenicity and activities of C7.

Goitrogenesis during pregnancy and neonatal hypothyroxinaemia in a borderline iodine sufficient area.

OBJECTIVE: Severe iodine deficiency disorders (IDDs) may have been eradicated in many parts of the world, but milder forms still exist and may escape detection. We evaluated the impact of pregnancy on the maternal and fetal thyroid axis in Hong Kong, a coastal city in southern China with borderline iodine intake. DESIGN: A prospective study performed in a maternity hospital. PATIENTS: Two hundred and thirty pregnant women were prospectively studied and their neonates assessed at birth. MEASUREMENTS: Urine iodine concentration, thyroid function tests and thyroid volume (TV) by ultrasound were determined in the mothers during pregnancy and up to 3 months postpartum and in the neonates. RESULTS: Increased urinary iodine concentration was seen from first trimester onwards and the proportion of women having urine iodine concentration of < 0.4 micromol/l decreased from 11.3% in the first trimester to 4.7% in the third trimester. There was progressive reduction in circulating fT4 and fT3 concentrations and free thyroxine index (FTI) with increasing gestation and the percentage of women having subnormal levels at term were 53.2%, 61.1% and 4.8%, respectively. The serum TSH concentration during pregnancy doubled towards term. In the first trimester, multiparous women had significantly larger TV than the nulliparous women (P < 0.001). By the third trimester, TV had increased by 30% (range 3-230%) so that the goitre incidence was 14.1%, 21.8%, 25.9% during the three trimesters of pregnancy, and 24.3% and 21.9% at 6 weeks and 3 months postpartum (ANOVA, P < 0.05). The change in thyroid volume during pregnancy correlated positively with the change in thyroglobulin (r = 0.225, P < 0.002) and negatively with urinary iodine concentration (r = - 0.149, P < 0.02). Fourteen women with excessive thyroidal stimulation in the second trimester (defined as those with thyroglobulin (Tg) concentrations in the highest tertile and FTI in the lowest tertile) were found to have lower urine iodine concentrations and larger TV (both P < 0.005) throughout pregnancy, and their neonates had higher cord TSH (P < 0.05), Tg (P < 0.05) and slightly larger TV (P = 0.06) as compared to the findings in 216 pregnant women without evidence of thyroid stimulation. Seven neonates (50%) born to these women had subnormal fT4 levels at birth. CONCLUSION: In a borderline iodine sufficient area, pregnancy posed an important stress resulting in higher rates of maternal goitrogenesis as well as neonatal hypothyroxinaemia and hyperthyro- trophinaemia. An adequate iodization program is necessary to eliminate iodine deficiency disorders during pregnancy.