Vomiting and hyponatraemia in pregnancy.
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Addison Disease↗
Biomedical subjects
L D Premawardhana
Publications and source records attributed to L D Premawardhana.
Postpartum thyroiditis and long-term thyroid status: prognostic influence of thyroid peroxidase antibodies and ultrasound echogenicity.
Postpartum thyroid dysfunction (PPTD) occurs in 5% of women, with hypothyroidism developing in 23% of these after 3-5 yr. We have determined the prognostic significance of thyroid peroxidase antibody (TPOAb), thyroid ultrasound morphology (U/S), human leukocyte antigen haplotype, and postpartum thyroid status on the development of thyroid dysfunction 77-81 months after PPTD. Ninety-eight TPOAb-positive [48 who had developed PPTD (group 1) and 50 without PPTD (group 2)] and 70 TPOAb-negative (group 3) women (derived from 145 TPOAb-positive and 229 TPOAb-negative cohorts at the index pregnancy), with comparable ages, parity, pregnancies after index pregnancy, and follow-up duration, were studied. Thyroid dysfunction occurred in 46% of group 1 vs. 4% of group 2 (P<0.001) and 24.5% of groups 1 and 2 vs. 1.4% of group 3 (P<0.001). Factors predictive of thyroid dysfunction included a hypothyroid form of PPTD, TSH more than 20 mU/L, and higher TPOAb levels (213.8 kIU/L in group 1 vs. 131.8 kIU/L in group 2; P<0.002) during the postpartum period. Although TPOAb was higher in group 1 than in group 2 at follow-up (166 vs. 97.7 kIU/L; P<0.03), there was no significant fall in TPOAb levels within either group during the period of follow-up. The prevalence of ultrasound hypoechogenicity was higher in group 1 than in group 2 at follow-up (76% vs. 52%; P<0.006), but U/S improved in 62.5% of group 1 during the period of follow-up. Human leukocyte antigen DR10 was lower in those who developed late thyroid dysfunction. These data, representing the longest follow-up of PPTD women, clearly show that the hypothyroid form of PPTD, high TPOAb levels, and a hypoechogenic U/S pattern lead to a high risk (relative risk, 32) of long term thyroid dysfunction. This compares with a relative risk of 12.9 for TPOAb- and PPTD-positive women, who remained euthyroid at the end of the first postpartum year, and 2.8 for TPOAb-positive but PPTD-negative women, all compared to TPOAb-negative women. Therefore, long term surveillance of TPOAb- and PPTD-positive women (group 1) is indicated.
Adult↗
Increased prevalence of thyroglobulin antibodies in Sri Lankan schoolgirls--is iodine the cause?
OBJECTIVE: Iodine deficiency was the likely cause of a high prevalence of goitre previously in Sri Lankan schoolchildren. Salt iodination was made compulsory in 1993 but there has been no recent study, using modern techniques, of its benefits or harmful effects. METHODS: Three hundred and sixty-seven schoolgirls between the ages of 11 and 16 years had ultrasound thyroid volume, free thyroxine (T4), free tri-iodothyronine (T3), thyrotrophin (TSH), anti-thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) antibodies, and urine iodine concentrations measured. RESULTS: Median ultrasound thyroid volume ranged from 4.8 ml (11-year-old girls) to 8.6 ml (16-year-old girls) with an age-related increase. Median urine iodine concentrations ranged from 105 to 152 microg/l. Free T4 and free T3 were normal in all, but TSH was elevated in four subjects (5. 53-41.29 mU/l). However, the prevalence of TgAb was markedly raised, ranging between 14.3% (11-year-old girls) and 69.7% (16-year-old girls) (P<0.03). In contrast, the prevalence of TPOAb was 10% or less in all age groups. CONCLUSIONS: Normal median thyroid volumes, iodine concentrations and thyroid function would indicate that iodine deficiency is not a major problem in this group. The high prevalence of TgAb, hitherto unreported, most likely reflects excessive iodination of Tg resulting in increased immunogenicity. There is an urgent need to continuously monitor the adequacy and risks of iodination in this population.
Adolescent↗
Screening for postpartum thyroiditis.
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Female↗
Longer term outcome in females with congenital adrenal hyperplasia (CAH): the Cardiff experience.
OBJECTIVE: The outlook for fertility and attaining full adult height is poor in women with congenital adrenal hyperplasia. Such outcomes have followed treatment regimes with variable ages at onset, compliance rates and monitoring. We review final height, vaginal anatomy, ovulation rates and fertility in a group of adult females with the disease. DESIGN AND PATIENTS: Sixteen adult females first diagnosed in infancy or early childhood were reviewed (age range 17-33 years; 11 with salt-wasting disease; five with simple virilizing disease). Case note and clinical review were combined with daily saliva progesterone and weekend 17-hydroxyprogesterone estimation in three consecutive menstrual cycles in a subgroup of eight patients in the ovulation study. MEASUREMENTS AND ANALYSIS: Daily saliva progesterone concentrations were transformed into a cumulative sum curve using a computer program. T95 (defined as the number of days from the start of the luteal phase saliva progesterone rise, in which 95% of total saliva progesterone for the menstrual cycle was obtained) and log C95 (where C95 was defined as 95% of total saliva progesterone for the same cycle) were plotted for each cycle on a boundary diagram obtained from a normal reference population. Weekend saliva 17-hydroxyprogesterone concentrations were compared with published nomograms. RESULTS: The majority of patients attained a final height below the parental target. Mean standard deviation scores (+/-SEM) and ranges were -1.49 (+/-0.34) and -4.2 to 0.8 for the patients and -0.38 (+/-0.24) and -1.89 to 0.97 for their parents. Of the combined group two-thirds had regular menses and one-third hirsutism; 94% had reconstructive genital surgery with 50% requiring second procedures; 77% had an adequate vaginal introitus (of them 84% in the salt-wasting group and 75% in the simple virilizing group were sexually active). Three of five patients with salt-wasting disease and 2/3 with simple virilizing disease who had both an adequate introitus and were sexually active conceived, resulting in eight pregnancies. In the ovulation study, a 40% ovulation rate was observed with good correlation between plasma testosterone concentrations and degree of control as assessed by weekend 17-hydroxyprogesterone concentrations. CONCLUSIONS: Our study highlights the potential for improved fertility in female patients with congenital adrenal hyperplasia, who are treated early, comply with long-term treatment and have adequately reconstructed external genitalia. Attaining full adult height potential remains a problem.
17-alpha-Hydroxyprogesterone↗
Variability of serum thyroglobulin levels is determined by a major gene.
OBJECTIVE: There are large variations in the circulating concentrations of thyroglobulin. The purpose of this study was to explore the possibility of a genetic basis for the variability of serum concentration of thyroglobulin (Tg) in euthyroid individuals. DESIGN: The serum concentration of thyroglobulin (Tg) varies several-fold in euthyroid individuals. Other circulating proteins also show wide normal ranges of concentration and these variations have been shown to have a genetic as well as an environmental basis. To explore the possibility of a genetic basis for variability in serum Tg levels, an analysis was made of serum Tg levels in 44 pairs of identical twins and 66 nuclear families who were euthyroid and thyroid autoantibody negative (thereby eliminating subclinical autoimmune thyroid disease and Tg autoantibody interference with the Tg assay). RESULTS: Each pair of identical twins tended to have a similar Tg level and the overall correlation was highly significant (r = 0.734, P < 0.001). There was no relation between Tg and TSH levels in the twins (r = 0.119; P = 0.366). Segregation analysis of the 66 families showed that where both parents had Tg levels above the overall median for the subjects (males, 19 micrograms/l; females, 33 micrograms/l), 73% of the offspring also had concentrations above these levels, compared with 30% of the offspring when one parent had a high Tg level and only 16% in families where neither parent had a high Tg level. CONCLUSIONS: Complex segregation analysis using the computer program Pointer suggested that variability in Tg levels was the result of a major dominant-like gene effect (accounting for 80% of the variability) combined with a multifactorial component. Thyroglobulin, a template for thyroid hormone production, is also a major thyroid autoantigen and inherited variations in serum Tg levels may have implications for the pathogenesis of autoimmune thyroid disease.
Adolescent↗
Acute cholinergic blockade with low dose pirenzepine reduces the insulin and glucose responses to a mixed meal in obese women with the polycystic ovary syndrome.
OBJECTIVES: Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal in a dose dependent fashion in normals and in patients with non-insulin dependent diabetes. We have studied the effects of pirenzepine on plasma insulin, plasma glucose, growth hormone (GH), androstenedione, testosterone, insulin-like growth factor-I (IGF-I) and IGF binding protein 1 (IGFBP-1) responses to a mixed meal in obese clinically hyperandrogenic women with the polycystic ovary syndrome. SUBJECTS AND METHODS: Six obese women with polycystic ovary syndrome (BMI range 27.3-39.8 kg/m2) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours. RESULTS: Mean fasting plasma insulin concentrations were increased. Peak post-prandial plasma insulin concentrations were reduced significantly by all three doses used. Post-prandial integrated plasma insulin concentrations were reduced by the two higher doses. Peak post-prandial plasma glucose concentrations were also reduced. The late post-prandial GH surge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF-I and IGFBP-1 concentrations were not significantly different when placebo was compared with pirenzepine 200 mg. CONCLUSIONS: Acute cholinergic muscarinic blockade with pirenzepine significantly reduces meal stimulated plasma insulin and plasma glucose concentrations in clinically hyperandrogenic women with polycystic ovary syndrome. The ability of pirenzepine to reduce plasma insulin without worsening glycaemia is a particular advantage and may be therapeutically relevant. Further studies are under way to assess the usefulness of pirenzepine in long-term suppression of plasma insulin in this group of patients.
Adult↗
Is TPO detectable in the circulation?
Recent reports have suggested that thyroid peroxidase (TPO) can be detected in the circulation of normal subjects and of patients with Graves' disease and we have attempted to confirm and extend these observations. A TPO radioimmunoassay with a sensitivity of 1 ng/mL was used to measure TPO in the sera from 20 normal subjects and 21 patients with Graves' disease. In addition, TPO was measured in serum samples from six normal subjects before and after oral TRH. We were unable to detect TPO in 46 out of the 47 sera studied (normals and autoimmune thyroid disease). In the one remaining serum (from a normal subject), low levels of TPO were apparently detected, but we demonstrated that this result was due to assay interference from TPO autoantibodies. Overall our studies suggest that (1) thyroid peroxidase is not detectable in normal subjects nor in TPO autoantibody negative patients with Graves' disease; (2) endogenous TPO autoantibodies can interfere in the TPO radioimmunoassay leading to false positive results; and (3) an acute increase of TSH in normal subjects does not result in TPO release into the circulation.
Adult↗
Genetic linkage analysis of thyroid autoantibodies.
Segregation analysis has suggested that the inheritance of thyroid autoantibodies (to thyroglobulin and to thyroid peroxidase) is a dominant Mendelian trait. In this study we describe an attempt to find the chromosomal location(s) of gene(s) responsible for thyroid autoantibody production. We have examined a number of restriction length polymorphisms (RFLPs) and highly polymorphic markers (mini- and microsatellite) for genetic linkage with thyroid autoantibodies using a panel of 16 families with autoimmune thyroid disease. None of the markers used in this study gave evidence of linkage, however minisatellite markers (MS1, MS31, MS32, MS43a, M851, G3) for TPO antibody, minisatellite markers (MS1, MS32, MS43a, MS51, G3) for Tg antibody, and all microsatellite markers used, provided evidence for exclusion of genetic linkage.
Adolescent↗
Acromegaly and its treatment in the McCune-Albright syndrome.
The McCune-Albright syndrome, comprising polyostotic fibrous dysplasia, cutaneous pigmentation and endocrine hyperfunction, is occasionally complicated by acromegaly due to a pituitary adenoma. We report a patient with the McCune-Albright syndrome and acromegaly, who developed secondary hypothyroidism and hypoadrenalism, in whom surgical removal of the pituitary tumour was technically difficult. A combination of a long-acting somatostatin analogue ('Sandostatin') and external irradiation were therefore used as treatment.
Acromegaly↗
Myotonia dystrophica--first presentation as severe left ventricular failure complicating dilated cardiomyopathy.
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Adult↗
Suppurative thyroiditis with oesophageal carcinoma.
A 68 year old, previously well woman presented with dysphagia, weight loss and a neck swelling. Investigations revealed a right-sided thyroid abscess with fistulous connection to the upper of two oesophageal carcinomas, a previously unreported association. The resistance of the thyroid to infection and the mechanisms of thyroid abscess formation in this patient are discussed.
Abscess↗