The interleukin-1 receptor antagonist gene shows no allelic association with three autoimmune diseases.
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Alleles↗
Biomedical subjects
M C Sheppard
Publications and source records attributed to M C Sheppard.
Outcome of surgery for acromegaly--the experience of a dedicated pituitary surgeon.
Previous large series of outcome following pituitary surgery for acromegaly, including our own, have demonstrated poor results, with cure, defined as GH <5 mU/l, achieved in only 33-42% of patients. In our previous series, surgery was performed by one of eight different surgeons. Largely based on the disappointing results of this previous audit of outcome, our practice since 1990 has been, whenever possible, to refer all patients with acromegaly to a dedicated pituitary surgeon (APJ). The objective of the current study was to re-analyse the outcome of surgical treatment for acromegaly since instituting this change. Tumour size and extension was determined on CT/MRI scanning. Biochemical cure was defined as a basal GH <5 mU/l or a nadir GH of <2 mU/l across an OGTT following initial pituitary surgery. Surgery was performed on 66 patients and 42 (64%) were cured, compared with 26/78 (33%) in our previous study (p<0.0005, chi (2) test). The cure rate for microadenomas (n=22) was 86%, and for macroadenomas 52%, compared with 54% (p<0.05, chi (2) test) and 30% (p<0.05, chi (2) test) respectively, in our previous study. We conclude that surgical outcome for acromegaly is enhanced if patients are operated on by a single experienced surgeon.
Acromegaly↗
Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by growth hormone and insulin-like growth factor: in vivo and in vitro studies.
The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11beta-hydroxysteroid dehydrogenase (11betaHSD), an oxo-reductase converting E to F (11betaHSD1) and a dehydrogenase (11betaHSD2) converting F to E. 11betaHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11betaHSD1 activity. In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20-40 mg/month for at least 12 months), GH rose from 7.1 +/- 1.5 to 17.5 +/- 4.3 mU/L (mean +/- SE), and insulin-like growth factor I (IGF-I) rose from 43.0 +/- 8.8 to 82.1 +/- 13.7 nmol/L (both P < 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 +/- 0.06 to 0.60 +/- 0.06; P < 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11betaHSD2 activity) suggested that this was due to inhibition of 11betaHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = -0.422; P < 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 +/- 49.2 to 29.3 +/- 15.4 mU/L; P < 0.01), the THF+allo-THF/THE ratio rose from 0.53 +/- 0.06 to 0.63 +/- 0.07 (P < 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio. In vitro studies conducted on cells stably transfected with either the human 11betaHSD1 or 11betaHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11betaHSD1 isozyme indicated a dose-dependent inhibition of 11betaHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11betaHSD2 activity. GH, through an IGF-I-mediated effect, inhibits 11betaHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11betaHSD1 expression.
11-beta-Hydroxysteroid Dehydrogenases↗
Thyroid receptor alpha1 and alpha2 mutations in nonfunctioning pituitary tumors.
We previously reported that nonfunctioning tumors of the anterior pituitary exhibit reduced expression of thyroid receptor (TR) alpha and beta isoforms, an observation that may account for abnormalities of T3-mediated negative regulation of the glycoprotein hormone common alpha-subunit. Reduced TR protein was associated with a parallel reduction in TRbeta messenger RNA (mRNA), although TRalpha1 and alpha2 mRNA levels were similar in nonfunctioning tumors and normal pituitaries. Because TRalpha shows aberrant posttranscriptional processing, and TRbeta is under ligand-dependent autoregulation, we hypothesized that aberrant TR expression in nonfunctioning tumors may reflect mutation in receptor coding and regulatory sequences, and therefore screened TRalpha mRNA and TRbeta T3 response elements and ligand binding domains for sequence anomalies. Screening TRalpha mRNA in 23 tumors and subsequently sequencing candidate fragments identified one silent change from published sequences and three novel missense mutations, two in the common TRalpha region (ser45ile and lys370asn) and one that was alpha2 specific (ser377leu). TRbeta response elements failed to show any differences from published sequences in 14 nonfunctioning tumors. Sequencing of TRbeta ligand binding domains were also identical to wild type in 23 nonfunctioning tumors. The functional significance of the novel TRalpha mutations is unknown; definition of mutant TR action may provide insight into the role of TRs in the growth control of pituitary cells.
Adult↗
The development of Graves' disease and the CTLA-4 gene on chromosome 2q33.
Case-control studies suggest that the CTLA-4 gene may be a susceptibility locus for Graves' disease. The previously reported A/G polymorphism at position 49 in exon 1 of the CTLA-4 gene was, therefore, investigated in a case-control (n = 743) and family-based (n = 179) dataset of white Caucasian subjects with Graves' disease. The relationship between CTLA-4 genotype and severity of thyroid dysfunction at diagnosis was also investigated. An increase in frequency of the G (alanine) allele was seen in Graves' patients compared with control subjects (42% vs. 31.5%, respectively; corrected P<0.0002; odds ratio = 1.58), and a significant difference in the distribution of GG, GA, and AA genotypes was observed between the groups (chi2 = 21.7; corrected P<0.00003). Increased transmission of the G allele was seen from heterozygous parents to affected offspring compared to unaffected offspring (chi2 = 5.7; P = 0.025). Circulating free T4 concentrations at diagnosis were significantly associated with CTLA-4 genotype (F = 3.26; P = 0.04). These results support the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders such as Graves' disease.
Abatacept↗
Characterization of 11beta-hydroxysteroid dehydrogenase activity and corticosteroid receptor expression in human osteosarcoma cell lines.
Studies in vitro and in vivo have shown that corticosteroids play an important role in bone physiology and pathophysiology. It is now established that corticosteroid hormone action is regulated, in part, at the pre-receptor level through the expression of isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which are responsible for the interconversion of hormonally active cortisol to cortisone. In this report we demonstrate 11beta-HSD activity in human osteoblast (OB) cells. Osteosarcoma-derived OB cell lines TE-85, MG-63 and SaOS-2 and fibrosarcoma Hs913T cells express the type 2 isoform of 11beta-HSD, as determined by reverse transcription polymerase chain reaction (RT-PCR) and specific enzyme assays. Enzyme activity was shown to be strictly NAD dependent with a Km of approximately 71 nM; 11beta-HSD type 1 mRNA expression and enzyme activity were not detected. All four cell lines expressed mRNA for the glucocorticoid receptor (GR) and mineralocorticoid receptor, but specific binding was only detectable with radiolabelled dexamethasone (Kd=10 nM) and not aldosterone. MG-63 cells had two to three times more GR than the other OB cells, which correlated with the higher levels of 11beta-HSD 2 activity in these cells. In contrast to the osteosarcoma cell studies, RT-PCR analysis of primary cultures of human OB cells revealed the presence of mRNA for 11beta-HSD 1 as well as 11beta-HSD 2. However, enzyme activity in these cells remained predominantly oxidative, i.e. inactivation of cortisol to cortisone (147 pmol/h per mg protein at 500 nM cortisol) was greater than cortisone to cortisol (10.3 pmol/h per mg protein at 250 nM cortisone). Data from normal human OB and osteosarcoma cells demonstrate the presence of an endogenous mechanism for inactivation of glucocorticoids in OB cells. We postulate that expression of the type 1 and type 2 isoforms of 11beta-HSD in human bone plays an important role in normal bone homeostasis, and may be implicated in the pathogenesis of steroid-induced osteoporosis.
11-beta-Hydroxysteroid Dehydrogenases↗
Mortality after the treatment of hyperthyroidism with radioactive iodine.
BACKGROUND: Hyperthyroidism affects many organ systems, but the effects are usually considered reversible. The long-term effects of hyperthyroidism on mortality are not known. METHODS: We conducted a population-based study of mortality in a cohort of 7209 subjects with hyperthyroidism who were treated with radioactive iodine in Birmingham, United Kingdom, between 1950 and 1989. The vital status of the subjects was determined on March 1, 1996, and causes of death were ascertained for those who had died. The data on the causes of death were compared with data on age-specific mortality in England and Wales. The standardized mortality ratio was used as a measure of relative risk, and the effect of covariates on mortality was assessed by regression analysis. RESULTS: During 105,028 person-years of follow-up, 3611 subjects died; the expected number of deaths was 3186 (standardized mortality ratio, 1.1; 95 percent confidence interval, 1.1 to 1.2; P<0.001). The risk was increased for deaths due to thyroid disease (106 excess deaths; standardized mortality ratio, 24.8; 95 percent confidence interval, 20.4 to 29.9), cardiovascular disease (240 excess deaths; standardized mortality ratio, 1.2; 95 percent confidence interval, 1.2 to 1.3), and cerebrovascular disease (159 excess deaths; standardized mortality ratio, 1.4; 95 percent confidence interval, 1.2 to 1.5), as well as fracture of the femur (26 excess deaths; standardized mortality ratio, 2.9; 95 percent confidence interval, 2.0 to 3.9). The excess mortality was most evident in the first year after radioiodine therapy and declined thereafter. CONCLUSIONS: Among patients with hyperthyroidism treated with radioiodine, mortality from all causes and mortality due to cardiovascular and cerebrovascular disease and fracture are increased.
Cardiovascular Diseases↗
Expression of oestrogen receptor and oestrogen-inducible genes pS2 and ERD5 in large bowel mucosa and cancer.
Since there is a preponderance of large bowel cancer in males, both in humans and in experimental models, and hormone replacement therapy is protective, a role for sex steroid hormones in the pathogenesis of this neoplasm seems likely. Evidence of functional oestrogen receptor has been looked for in large bowel mucosa and cancer. Expression of oestrogen receptor, and of the oestrogen-inducible receptor-associated genes pS2 and ERD5, was sought. Oestrogen receptor mRNA was detected in cancers and paired normal mucosae in equal amounts. In situ hybridization identified stromal cells above the muscularis mucosae that were positive for oestrogen receptor mRNA. pS2 mRNA was also detected, with a signal intensity significantly higher in normal mucosa compared with cancers, whereas the reverse was seen with ERD5 mRNA levels. pS2 and ERD5 were expressed in epithelium, with the former in a greater amount in distal colon and rectum than proximal colon. Although oestrogen-inducible and receptor-associated genes are expressed in large bowel mucosa, their expression does not correlate with oestrogen receptor.
Aged↗
Retinoid X receptor expression in the normal pituitary and clinically 'non-functioning' pituitary tumours.
OBJECTIVE: The glycoprotein hormone common alpha-subunit is frequently expressed in clinically 'non-functioning' tumours (NFTs) of the anterior pituitary, despite normal levels of T3 and gonadal steroids. This observation suggests abnormal negative-feedback regulation of the alpha-subunit by T3 and gonadal steroids in NFTs. We have previously documented reduced expression of thyroid hormone receptor (TR) variants in NFTs compared to normals and proposed that this observation may, in part, explain the defective negative regulation. Due to the important role of retinoid X receptors (RXRs) in transactivating TR-mediated transcriptional regulation, via heterodimer formation, we hypothesize that aberrant RXR isoform expression in NFTs may contribute to the defective negative regulation of the alpha-subunit by T3. DESIGN: Comparison of RXR isoform protein and mRNA expression in NFTs and normal pituitaries. PATIENTS AND TUMOURS: Twenty clinically non-functioning pituitary tumours and 27 normal pituitaries were obtained for analysis. MEASUREMENTS: Immunocytochemistry and semiquantitative RT-PCR was performed on tumours and normal pituitaries to determine the relative levels of expression of RXR isoform proteins and mRNAs, respectively. RESULTS: RXR alpha was expressed in a similar proportion (approximately 50%) of both normal human pituitaries and NFTs, while RXR beta and gamma were each observed in 26% of normals but were undetectable in NFTs. The application of semiquantitative RT-PCR revealed similar levels of mRNAs encoding the RXR alpha and RXR beta isoforms in normals and NFTs but significantly reduced expression of RXR gamma mRNA was observed in NFTs. CONCLUSIONS: We propose that abnormal RXR isoform expression in clinically 'non-functioning' pituitary tumours may contribute to abnormal T3-mediated negative regulation of alpha-subunit production.
DNA-Binding Proteins↗
Long-term therapy with long-acting octreotide (Sandostatin-LAR) for the management of acromegaly.
OBJECTIVES: To evaluate the efficacy and safety of a long-acting preparation of the somatostatin analogue octreotide, Sandostatin-LAR (SMS-LAR) for the treatment of acromegaly. DESIGN AND PATIENTS: Thirteen patients with acromegaly received intramuscular injections of SMS-LAR 20-40 mg at 4-6 week intervals for a period of up to 3 years. MEASUREMENTS: Serial measurement of serum GH and IGF concentrations were obtained. Symptoms related to acromegaly were scored by patients at baseline and following each injection. Serial gallbladder ultrasound and pituitary imaging was performed throughout the study. RESULTS: One patient was withdrawn from the study after 6 months because of continued gastrointestinal side effects; 4 patients were treated with monthly injections for 12 months and 8 patients with injections at either 1 month or 6-week intervals for 36 months; hence data is presented for n = 12 for up to 12 months; and thereafter n = 8. SMS-LAR significantly reduced serum GH and IGF-1 values: for the whole group GH concentrations fell from 24.8 +/- 4.2 mU/l (mean +/- SE) at baseline to 5.2 +/- 0.8 mU/l at 12 months (P < 0.01, n = 12). In the 8 patients treated for 3 years GH fell from 27.8 +/- 6.1 mU/l at baseline to 4.2 +/- 0.8 mU/l at the end of 3 years (P < 0.01, n = 8). GH fell to < 10 mU/l in all subjects and was < 5 mU/l in 50% after both 1 and 3 years. IGF-1 concentrations fell from 95 +/- 13 nmol/l at baseline to 63 +/- 13 nmol/l after 1 year (P < 0.01, n = 12; reference range < 65 nmol/l). In the 8 patients treated for 3 years IGF-1 concentrations fell from 119 +/- 14 nmol/l at baseline to 60 +/- 13 nmol/l after 3 years (P < 0.001, n = 8). IGF-1 was < 65 nmol/l in 60% of patients after 1 year and 75% after 3 years. Treatment resulted in trends towards improvement in symptoms of acromegaly and statistically significant improvement in sweating. There was no evidence of tachyphylaxis or evidence to suggest development of glucose intolerance. Only 2 patients (15%) developed gallbladder sludge which was asymptomatic; no patient developed gallstones. CONCLUSIONS: We conclude that SMS-LAR is a safe, effective and well tolerated treatment, making it an important therapeutic option in the management of acromegaly.
Acromegaly↗
Radiotherapy for non-function pituitary tumours.
OBJECTIVE: Pituitary radiotherapy (RT) is often used as adjuvant treatment in the post-operative period for patients with clinically non-functioning pituitary tumours (NFTs). There is a distinct lack of objective data, however, describing the efficacy of RT in preventing the regrowth of these tumours. We have therefore determined whether the recurrence rate for NFTs is significantly lower in patients treated with post-operative RT compared with that observed in patients not treated with RT. PATIENTS AND METHODS: A retrospective case notes review was performed on 126 patients with NFTs treated at two institutions in the UK. One hospital routinely administered RT within 12 months of initial pituitary surgery whereas the other used post-operative RT only rarely. The main outcome measure was regrowth of pituitary tumours following surgery in patients who did or did not receive post-operative RT. RESULTS: There was no significant difference between patients who received RT versus those who did not in terms of age, sex, initial tumour size or mode of operation. The actuarial progression-free survival was 93% at both 10 years and at 15 years for the RT treated group, and was 68% and 33%, respectively, for the non-RT-treated group. Using Cox's model for proportional hazard analysis, we found the only prognostic factor for NFT regrowth was the administration of pituitary RT (P < 0.00005). CONCLUSIONS: Radiotherapy administered within 12 months of initial pituitary surgery for non-functioning pituitary tumours significantly reduces the risk of tumour regrowth. It remains to be determined whether sequential MRI scanning can help delineate those patients who should receive radiotherapy following pituitary surgery for non-functioning pituitary tumours.
Adult↗
Retinoid X receptor gamma mRNA expression is reduced in recurrent non-functioning pituitary adenomas.
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Adenoma↗
Defining the normal cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-pituitary disorders.
OBJECTIVE: To define the normal cortisol response to the Short Synacthen Test using four different cortisol immunoassays and to assess the implications for the investigation of hypothalamic-pituitary disorders. DESIGN AND PATIENTS: The cortisol response to 250 micrograms im ACTH1-24 (Synacthen, Ciba Geigy) in 100 healthy volunteers using four different cortisol immunoassays has been measured. In 44 newly diagnosed and untreated patients with pituitary disease, basal and 30 minute post-ACTH cortisol results were also determined using the four immunoassays. RESULTS: The distribution of cortisol results at all time points and for all methods were non-Gaussian and significant differences in the absolute values of the 5th-95th percentiles were found between methods (P < 0.01). At 30 min post-Synacthen in normals the 5th percentile of the cortisol response ranged from 510 to 626 nmol/l with the different methods. Similarly the relationship between assay results differed at different time points. No effect of age on the cortisol response was found but for stimulated cortisol values and the incremental responses females showed significantly higher responses than males (P < 0.05) for most methods. Although there was a significant positive linear correlation (P < 0.001) between stimulated and basal cortisol values for all methods, no significant relationship was found between the incremental response and basal cortisol values. In the pituitary disease patients basal and 30 minute post-ACTH cortisol results were significantly lower (P < 0.05 and < 0.001) than the control group using the same cortisol assay. When the results were compared to the 5th percentile of the gender and assay specific control group 33.3% of male and 17.4% of female patients failed the Synacthen test at 30 min. CONCLUSIONS: The definition of the 'normal' response to Synacthen should be both gender and method related at all time points. The data suggest that up to one-third of untreated patients with pituitary disease may have subtle defects in the hypothalamic-pituitary-adrenal axis.
Adult↗
Comparison of the short ACTH stimulation test with the insulin tolerance/glucagon test.
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Adrenocorticotropic Hormone↗
Differential regulation of the human thyrotropin alpha-subunit promoter by thyroid hormone receptors alpha1 and beta1.
The differential tissue expression of thyroid hormone receptor (TR) isoforms implies that they fulfil different roles in mediating triiodothyronine (T3) regulation. We have examined the differential roles of TR isoforms in mediating T3-dependent repression of the human thyrotropin (TSH)-alpha subunit gene promoter in vitro, and have assessed TR binding characteristics using gel mobility shift assays. Expression of transfected TR in JEG-3 cells revealed that TRalpha1 and TRbeta1 differentially inhibited TSHalpha subunit expression in the presence of T3, with TRbeta1 twice as potent as TRalpha1. TRalpha2 antagonized T3-dependent repression when coexpressed with TRalpha1 and TRbeta1. Gel mobility shift assays, performed in the presence and absence of JEG-3 nuclear extract, demonstrated that TRbeta1 bound with higher affinity to the wild-type TSHalpha negative thyroid hormone response element (nTRE) than TRalpha1. In vivo, the differential DNA binding of TR variants to nTREs may determine the ability of receptors to mediate T3-dependent repression.
Cell Line↗
Lack of association between polymorphism of the thyrotropin receptor gene and Graves' disease in United Kingdom and Hong Kong Chinese patients: case control and family-based studies.
The thyrotropin receptor (TSH-R) gene is a candidate for genetic susceptibility to Graves' disease (GD). Previous case control studies investigating allelic association of a polymorphism at position 253 (C253 to A253) of the TSH-R gene have shown conflicting results. We genotyped two independent case control datasets (UK Caucasian and Hong Kong Chinese), for the A253 polymorphism. The Transmission Disequilibrium Test was also used in a third family-based dataset that included 89 UK Caucasian families (both parents, a GD sibling and an unaffected sibling). Genotyping was performed by polymerase chain reaction (PCR)-amplification of genomic DNA and Tth111 I restriction enzyme digestion. No difference in frequencies of the A253 polymorphism between GD (21/204, 10.3%) and controls (34/358, 9.5%) was found in the UK Caucasians (chi2 = 0.093; p = NS). A similar finding was observed in GD (0/96, 0%) and controls (2/71, 2.8%) in Hong Kong Chinese subjects (chi2 = 2.73; p = NS). Results from the 89 UK families showed no deviation from the expected transmission frequency of 0.5, from parents heterozygous for the A253 allele to either Graves' or unaffected offspring (Fisher's exact test p = 0.22) and, therefore, confirmed a lack of evidence of linkage disequilibrium between the A253 allele and GD.
Alleles↗
An abnormality of thyroid hormone receptor expression may explain abnormal thyrotropin production in thyrotropin-secreting pituitary tumors.
Thyrotropin (TSH)-secreting pituitary adenomas cause hyperthyroxinemia in the presence of "inappropriately" elevated concentrations of TSH. TSH production under these circumstances escapes the normal negative feedback effect of thyroid hormone. We propose that this defective negative feedback is mediated by an abnormality of thyroid hormone receptor (TR) expression. Two TSH-secreting pituitary adenomas were analyzed by immunocytochemistry for TR isoform protein expression and by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) for TR isoform mRNA expression. The results obtained from these tumors were compared with the findings from six normal human pituitaries. Neither tumor examined expressed detectable levels of nuclear TRalpha or TRbeta proteins, in contrast to the normal pituitaries studied, which expressed all TR isoforms. Application of RT-PCR, however, revealed mRNAs encoding each TR isoform in all tumorous and normal tissues examined. Semiquantitative RT-PCR revealed similar levels of expression of TRalpha and TRbeta isoform mRNAs in tumors and normal tissue, in contrast to the observed difference in TR proteins. Absent TRalpha and TRbeta protein expression, in association with normal mRNA levels, implies a post-transcriptional defect in TR mRNA processing in TSH-secreting adenomas. Reduced TR expression in these tumors may explain defective negative feedback of thyroid hormone on TSH production, and may also contribute to uncontrolled tumor growth.
Adenoma↗
Measurement of serum TSH in the investigation of patients presenting with thyroid enlargement.
In otherwise euthyroid patients presenting with thyroid enlargement, reduction in serum thyrotrophin (TSH) concentrations measured in a sensitive assay may be a marker of thyroid autonomy and may therefore indicate a benign underlying pathology. We investigated prospectively a cohort of 467 subjects presenting consecutively to our thyroid clinic with nodular or diffuse enlargement of the thyroid. Subjects were divided into those with normal (0.4-5.5 mU/l), low but detectable (0.1-0.39 mU/l) or undetectable (< 0.1 mU/l) serum TSH concentrations. The final pathological diagnosis was defined by fine-needle aspiration cytology and clinical follow-up of at least 2 years or by fine-needle aspiration cytology and histology following surgical treatment. Serum TSH concentrations below normal were found in 75 patients (16.1%), those with low serum TSH results having higher mean free T4 concentrations, were older and were more likely to be female. In those with undetectable serum TSH, no patient had a diagnosis of thyroid neoplasia and in those with low but detectable TSH, thyroid neoplasms were diagnosed in two patients (3.4%). In those with normal serum TSH, 12.0% had a final diagnosis of thyroid neoplasm (p = 0.013). Overall, thyroid malignancy was found in one patient (1.3%) of those with a serum TSH measurement below the normal range and 6.9% of those with normal serum TSH (p < 0.06). Reduction in serum TSH at presentation may identify a group which requires less intensive investigation and follow-up than those without biochemical evidence of thyroid autonomy.
Biomarkers↗