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M C Sheppard

Publications and source records attributed to M C Sheppard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Tie-2 is expressed on thyroid follicular cells, is increased in goiter, and is regulated by thyrotropin through cyclic adenosine 3',5'-monophosphate.

Angiogenesis is coordinated with follicular cell growth in goitrogenesis. The angiopoietins, Ang-1 and Ang-2, are angiogenic growth factors acting through Tie-2, a tyrosine kinase receptor. We have examined the expression and regulation of the angiopoietins and Tie-2 in human and rat thyroids. In human goiters there was increased Tie-2 immunostaining, compared with that in normal thyroids, on both follicular and endothelial cells. In an induced goiter in rats, in situ hybridization showed increased expression of messenger ribonucleic acids (mRNAs) for Tie-2 and Ang-1 in follicular cells. As Tie-2 has previously been believed to be restricted to cells of endothelial lineage in adults, we examined its expression further in isolated follicular cells. Tie-2 and Ang-1 mRNA expression in human thyrocytes was confirmed by ribonuclease protection assay. Ang-2 mRNA was not detected in human cultures or rat thyroids. In both human follicular cell cultures and FRTL-5 cells, immunoblotting showed that Tie-2 expression was increased by TSH and agents that increased intracellular cAMP. In conclusion, we have demonstrated the expression of Tie-2 and Ang-1 in thyroid epithelial and endothelial cells, and have shown the regulation of Tie-2 by TSH and cAMP in follicular cells. Tie-2 expression is increased in goiter in both humans and rats, consistent with a role in goitrogenesis.

Angiopoietin-1↗
PubMed2001

Radioiodine treatment of hyperthyroidism-prognostic factors for outcome.

There is little consensus regarding the most appropriate dose regimen for radioiodine (131I) in the treatment of hyperthyroidism. We audited 813 consecutive hyperthyroid patients treated with radioiodine to compare the efficacy of 2 fixed-dose regimens used within our center (185 megabequerels, 370 megabequerels) and to explore factors that may predict outcome. Patients were categorized into 3 diagnostic groups: Graves' disease, toxic nodular goiter, and hyperthyroidism of indeterminate etiology. Cure after a single dose of 131I was investigated and defined as euthyroid off all treatment for 6 months or T4 replacement for biochemical hypothyroidism in all groups. As expected, patients given a single dose of 370 megabequerels had a higher cure rate than those given 185 megabequerels, (84.6% vs. 66.6%, P < 0.0001) but an increase in hypothyroidism incidence at 1 yr (60.8% vs. 41.3%, P < 0.0001). There was no difference in cure rate between the groups with Graves' disease and those with toxic nodular goiter (69.5% vs. 71.4%; P, not significant), but Graves' patients had a higher incidence of hypothyroidism (54.5% vs. 31.7%, P < 0.0001). Males had a lower cure rate than females (67.6% vs. 76.7%, P = 0.02), whereas younger patients (<40 yr) had a lower cure rate than patients over 40 yr old (68.9% vs. 79.3%, P < 0.001). Patients with more severe hyperthyroidism (P < 0.0001) and with goiters of medium or large size (P < 0.0001) were less likely to be cured after a single dose of 131I. The use of antithyroid drugs, during a period 2 wk before or after 131I, resulted in a significant reduction in cure rate in patients given 185 megabequerels 131I (P < 0.01) but not 370 megabequerels. Logistic regression analysis showed dose, gender, goiters of medium or large size, and severity of hyperthyroidism to be significant independent prognostic factors for cure after a single dose of 131I. We have demonstrated that a single fixed dose of 370 megabequerels 131I is highly effective in curing toxic nodular hyperthyroidism as well as Graves' hyperthyroidism. Because male patients and those with more severe hyperthyroidism and medium or large-sized goiters are less likely to respond to a single dose of radioiodine, we suggest that the value of higher fixed initial doses of radioiodine should be evaluated in these patient categories with lower cure rates.

Adolescent↗
PubMed2001

Modulation of 11beta-hydroxysteroid dehydrogenase isozymes by proinflammatory cytokines in osteoblasts: an autocrine switch from glucocorticoid inactivation to activation.

Tissue damage by proinflammatory cytokines is attenuated at both systemic and cellular levels by counter anti-inflammatory factors such as corticosteroids. Target cell responses to corticosteroids are dependent on several factors including prereceptor regulation via local steroidogenic enzymes. In particular, two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), by interconverting hormonally active cortisol (F) to inactive cortisone (E), regulate the peripheral action of corticosteroids 11beta-HSD1 by converting E to F and 11beta-HSD2 by inactivating F to E. In different in vitro and in vivo systems both 11beta-HSD isozymes have been shown to be expressed in osteoblasts (OBs). Using the MG-63 human osteosarcoma cell-line and primary cultures of human OBs, we have studied the regulation of osteoblastic 11beta-HSD isozyme expression and activity by cytokines and hormones with established roles in bone physiology. In MG-63 cells, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) potently inhibited 11beta-HSD2 activity (cortisol-cortisone conversion) and messenger RNA (mRNA) levels in a dose-dependent manner while stimulating reciprocal expression of 11beta-HSD1 mRNA and activity (cortisone-cortisol conversion). A similar rise in 11beta-HSD1 reductase activity also was observed in primary cultures of OBs treated with 10 ng/ml TNF-alpha. Pretreatment of MG-63 cells with 0.1 ng/ml IL-1beta resulted in increased cellular sensitivity to physiological glucocorticoids as shown by induction of serum and glucocorticoid-inducible kinase (SGK; relative increase with 50 nM F but no IL-1beta pretreatment 1.12 +/- 0.34; with pretreatment 2.63 +/- 0.50; p < 0.01). These results highlight a novel mechanism within bone cells whereby inflammatory cytokines cause an autocrine switch in intracellular corticosteroid metabolism by disabling glucocorticoid inactivation (11beta-HSD2) while inducing glucocorticoid activation (11beta-HSD1). Therefore, it can be postulated that some of the effects of proinflammatory cytokines within bone (e.g., periarticular erosions in inflammatory arthritis) are mediated by this mechanism.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.

BACKGROUND: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. METHODS: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. RESULTS: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups. CONCLUSIONS: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Acromegaly↗
PubMed2000

Follow-up of treated acromegaly: similarities and differences in assessing the response to different primary treatment modalities.

The decreased survival rate previously reported in patients with acromegaly can be normalized by successful surgical and adjunctive therapy. After surgical treatment, however, abnormalities of pulsatile growth hormone (GH) secretion may persist in spite of normal insulin-like growth factor I (IGF-I) levels, and there is a significant relapse rate. Radiotherapy is effective in lowering GH levels but relatively ineffective in normalizing IGF-I levels. There are very few data on long-term outcome after medical treatment of acromegaly, although current studies of patients receiving primary medical therapy will produce further information. IGF-I level may become an increasingly important biochemical end point. The goal of therapy is to achieve a biochemical value that reverses both the morbidity and increased mortality rate without resulting in hypopituitarism.

Acromegaly↗
PubMed2000

The renal expression of transforming growth factor-beta isoforms and their receptors in acute and chronic experimental diabetes in rats.

Transforming growth factors-beta (TGF-beta) are fibrogenic factors that have been strongly implicated in the development of diabetic nephropathy. Our aim was to use two animal models [the streptozotocin (STZ)-induced diabetic rat and the genetically prone biobreeding (BB) rat] to fully characterize the responses of the renal TGF-beta system in both short- and long-term diabetes. In this study changes in the entire renal TGF-beta system, at both protein and messenger RNA (mRNA) levels, have been characterized using the techniques of immunocytochemistry, Western blotting, and ribonuclease protection assay. We also used Western blotting of pro-collagen-I C-peptide to demonstrate that the rate of fibrogenesis was highest over the first 2 weeks of diabetes. TGF-beta1, TGF-beta2, and receptor mRNA and protein were detected in the control nondiabetic kidney. It was found that dramatic and dynamic changes occur in all parts of the renal TGF-beta axis in both models of experimental diabetes, but TGF-beta2 and TGF-betaRII proteins were the predominant responsive element, particularly during the acute phase of disease. For example, during the acute phase of disease (0-30 days), although renal TGF-beta1 mRNA levels were elevated, no increases in the corresponding protein were detected in the kidney. By contrast, in the absence of changes in TGF-beta2 mRNA levels, twice as much TGF-beta2 protein was measured in the kidney by day 30 of STZ-induced diabetes compared with day 0 controls analyzed by Western blotting (P < 0.05), and the protein was localized both to the nuclei and cytoplasm of glomerular cells, analyzed by immunocytochemistry. In addition, three times as much TGF-betaRII protein was found by day 90 of STZ-induced diabetes compared with day 0 controls, making this the most responsive receptor type. These results suggest that the entire TGF-beta axis has a role in the etiology of kidney fibrosis and could be manipulated therapeutically to preserve kidney function.

Albuminuria↗
PubMed2000

Age and gender predict the outcome of treatment for Graves' hyperthyroidism.

The response to treatment in Graves' hyperthyroidism is unpredictable, and factors postulated to predict outcome have not generally proved clinically useful or been widely adopted in clinical practice. We audited outcome in 536 patients with Graves' hyperthyroidism presenting consecutively to determine whether simple clinical features predict disease presentation and response to treatment. At presentation males had slightly more severe biochemical hyperthyroidism [free T4: males, 64.3 +/- 3.0 pmol/L (mean +/- SE); females, 61.3 +/- 1.7 (P = 0.45); free T3: males, 24.3 +/- 1.5 pmol/L; females, 21.0 +/- 0.6, (P = 0.04)]. Patients less than 40 yr at diagnosis had more severe hyperthyroidism than patients more than 40 yr old [free T4: <40 yr, 64.3 +/- 2.0; >40 yr, 56.7 +/- 2.3 (P = 0.02); free T3: <40 yr, 22.8 +/- 0.8; >40 yr, 19.0 +/- 0.9 (P = 0.003)]. Males had a lower remission rate than females after a course of antithyroid medication [19.6% vs. 40%; odds ratio, 0.37; 95% confidence interval (CI), 0.17-0.79; P < 0.01]. Similarly, patients aged less than 40 yr had a lower remission rate than older patients (32.6% vs. 47.8%; odds ratio, 0.53; 95% CI, 0.32-0.87; P = 0.01). One dose of radioiodine cured hyperthyroidism in fewer males than females (47% vs. 74%; P < 0.0001). Logistic regression analysis demonstrated male sex (odds ratio, 2.80; 95% CI, 1.31-5.98; P = 0.008), serum free T4 concentration at diagnosis (odds ratio, 1.02; 95% CI, 1.0-1.04; P = 0.01), and dose of radioiodine administered (odds ratio, 0.99; 95% CI, 0.99-1.00; P = 0.001) were contributing factors associated with failure to respond to a single dose of radioiodine. As males and younger patients are more likely to fail to respond to medical treatment, and male patients are likewise less likely to respond to a single dose of radioiodine, we suggest that those groups with low remission rates should be offered definitive treatment with radioiodine or surgery soon after presentation and that the value of higher initial doses of radioiodine in males be evaluated.

Adolescent↗
PubMed2000

Apoptosis during goitre involution - the role of Bcl-2.

Goitrogenesis is accompanied by hyperplasia and hypertrophy and involves tissue remodelling and angiogenesis. During the involution of the goitre there must be removal of this increased thyroid volume, in addition to further remodelling, which may involve apoptosis. We investigated apoptosis in the involuting rat thyroid using male Fisher rats that were on a goitrogenic regimen for 14 days and then returned to a normal diet. Thyroid weights increased fourfold with the goitrogenic regimen. During involution, the largest decrease in weight was between day 2 and day 4 after withdrawal of treatment. After 34 days of involution, the thyroid weight plateaued, but had not returned to control values. High levels of Bcl-2 immunoreactivity were observed in normal and goitrous rat thyroids. These high levels were significantly reduced at 2 days of involution, after which high levels of Bcl-2 immunoreactivity returned. In situ end-labelling of apoptotic cells showed that there was an increase in the number of cells undergoing DNA fragmentation during goitrogenesis (1.0+/-0.8 cells/100 cells, n=9) compared with controls, in which no positive staining was observed. After 2 days of goitrogen withdrawal, there was a further fourfold increase in the number of in situ end-labelled cells (day 16: 4.1+/-1.7, n=9). Numbers of positive cells returned to low levels after 4 days of involution (day 18: 0.3+/-0.8, n=9). Using antiserum to apoptosis-specific protein, we found increased immunoreactivity during goitrogenesis and after 2 days of involution that was localised predominantly with the stromal and vascular tissue at both time points. The data show that rapid downregulation of Bcl-2 accompanies thyroid involution, which involves increased levels of apoptosis within the stromal compartment.

Animals↗
PubMed1999

Estrogen receptor beta mRNA expression in normal and adenomatous pituitaries.

Estrogen (E2), acting via its nuclear receptors, has been implicated in tumor development and growth, particularly in the pathogenesis of breast cancer. E2 also modulates anterior pituitary hormone production and is a potent cell mitogen. Until recently, the actions of E2 were thought to be mediated by a single estrogen receptor (ER) isoform (ER alpha), and currently little is known of the pathophysiological relevance of the ER beta isoform. The presence of ER beta mRNA has been demonstrated by RT-PCR in the normal human pituitary, although expression of ER beta mRNA in human pituitary tumors has now been described. We have used semiquantitative RT-PCR to determine the relative levels of expression of ER beta mRNA in normal human pituitaries, non-functioning pituitary adenomas and GH-secreting tumors. ER beta mRNA was detected in normal pituitaries and all pituitary tumors examined. The ratio of ER beta mRNA to beta-actin mRNA expression was significantly reduced in non-functioning pituitary tumors (NFTs; 0.92 +/- 0.09; mean +/- SE; n = 23) compared with findings in normal pituitaries (1.56 +/- 0.21; mean +/- SE; n = 5; p < 0.05 Student's t-test). Studies of ER beta protein expression are required to determine the functional significance of reduced ER beta mRNA expression in NFTs.

Adenoma↗
PubMed1999

The therapeutic value of somatostatin and its analogues.

In this review we discuss the physiological effects of somatostatin, which are mediated by specific receptor subtypes on different tissues. These observations have suggested new therapeutic possibilities for the use of the synthetic somatostatin analogues in the treatment of acromegaly as well as a number of other endocrine and non-endocrine disorders.

Acromegaly↗
PubMed1999

Life expectancy following surgery for pituitary tumours.

OBJECTIVE: Hypopituitarism, predominantly although not exclusively due to nonfunctioning pituitary tumours, has been associated with reduced life expectancy. Mortality from vascular diseases contributed significantly to the overall increase in mortality in some, but not all of the studies published to date. The aim of this study was to contribute further data to the debate regarding the putative association of vascular mortality with hypopituitarism. DESIGN AND PATIENTS: A retrospective case note review of patients undergoing pituitary surgery in Birmingham, between 1/1/70 and 1/1/92. Subjects were identified from neurosurgical and neuropathology records. 348 patients were identified of which 197 were male (median age at surgery 48.4, range 11-79 years) and 151 female (median age at surgery 47.8, range 9-78 years). All cause mortality and mortality from vascular disease was compared to the general population of the UK using the Person Years computer programme. RESULTS: There was a small increase in all cause mortality (SMR 1.2; 95% CI 0.95-1.55), but this was not statistically significant in this study (P = 0.06). Mortality from vascular disease was reduced (SMR 0.7; 95% CI 0.5-1.1; P = 0.03) particularly in the female cohort (SMR 0.5; 95% CI 0.2-1.0; P < 0.01) with the male subjects having similar mortality to that expected in an age and sex matched control population (SMR 0.9; 95% CI 0.5-1.4; P = 0.26). CONCLUSION: Although patients with pituitary deficiency may be subject to a small increase in all cause mortality, the results of this study do not support the view that hypopituitarism is associated with a significant increase in vascular disease. There is a pressing need for a large prospective study with comprehensive data collection, including both endocrine data and information regarding clinical outcome, to clarify this issue. In the interim it would seem prudent to base the need for GH replacement therapy on quality of life issues rather than any potential for increased longevity.

Adolescent↗
PubMed1999

Clinical and biochemical response following withdrawal of a long-acting, depot injection form of octreotide (Sandostatin-LAR).

OBJECTIVE: Monthly injections of Sandostatin-LAR have been shown to be an effective therapy for patients with acromegaly. Because of an ongoing need to assess a patients response to definitive therapy such as surgery and/or radiotherapy, we aimed to evaluate GH levels and acromegaly symptom scores in patients withdrawing from Sandostatin-LAR. DESIGN AND PATIENTS: 12 patients with acromegaly previously treated with Sandostatin-LAR, 20-40 mg intramuscularly every 28 (n = 9) or 42 (n = 3) days for 12-36 months were studied at monthly intervals for 4 months following the withdrawal of the drug. MEASUREMENTS: Hourly fasting serum GH measurements between 0800 h and 1200 h, serum IGF-1 and symptom scores were undertaken at 4, 8, 12 and 16 weeks following the last injection of Sandostatin-LAR. MRI/CT scans of the pituitary were undertaken at 16 weeks and compared to scans taken on Sandostatin-LAR within the previous 10 months. RESULTS: Serum GH rose progressively from 7.7 (1.5 to 14.6) (median (range)) mIU/l at 4 weeks to 9.9 (1.5-21.8), to 12.6 (4.9-31.9) (P < 0.05 vs 4 weeks) and to 13.1 (6.0-39.1) mIU/l (P < 0.002) at 8, 12 and 16 weeks, respectively, following cessation of Sandostatin-LAR. IGF-1 rose from 38.5 (12.6-73.8) nmol/l at 4 weeks to 62.4 (37.4-159) at 16 weeks (P < 0.002) and mean symptom score (comprising headache, sweating, arthralgia, paraesthesiae, tiredness) from 4.0 (0 to 10) (4 weeks) to 4.5 (0-9) (8 weeks) to 6.0 (2-10) (12 weeks) to 6.5 (4-12) (16 weeks, P < 0.05). Individual GH profiles indicated a rise in GH in 5/12 patients between weeks 4-8 and between weeks 8-12 in a further 5/12 patients. There were no changes in pituitary tumour size following discontinuation of Sandostatin-LAR. CONCLUSIONS: GH and symptom scores rise progressively following discontinuation of Sandostatin-LAR in acromegalic patients. However, GH and symptom scores remain suppressed in some patients for at least 8 weeks following cessation of Sandostatin-LAR. We suggest that a withdrawal period of 3 months from Sandostatin-LAR is required in order to perform a meaningful re-assessment of GH and clinical status.

Acromegaly↗
PubMed1999

Increased MEN1 mRNA expression in sporadic pituitary tumours.

BACKGROUND: The MEN1 gene on chromosome 11q13 encodes a tumour suppressor gene, mutations in which cause multiple endocrine neoplasia (MEN) type 1 syndrome. Loss of heterozygosity (LOH) at this locus is a common finding amongst sporadic pituitary tumours. We have therefore screened the MEN1 gene for mutations in sporadic pituitary tumours and, as the gene is a putative tumour suppressor, have quantified mRNA expression in tumorous and normal pituitaries to assess the role of MEN1 in pituitary tumorigenesis. SUBJECTS AND DESIGN: Thirty-one nonfunctioning pituitary tumours, 8 GH secreting, 2 TSH-secreting tumours and 1 corticotrophinoma have been assessed for the presence of MEN1 mutations, to examine the hypothesis that MEN1 mutations may contribute to the pathogenesis of sporadic pituitary neoplasms. In addition, quantitative changes in the pretranslational expression of the tumour suppressor gene MEN1 have been determined in 42 pituitary tumours and 6 normal pituitaries using semiquantitative reverse transcriptase PCR. RESULTS: No novel or previously published mutations were apparent in the MEN1 coding regions of any tumours studied, although several polymorphisms were identified. Transcriptional changes of the gene, assessed by semiquantitative RT-PCR, indicated that nonfunctioning and GH-secreting pituitary tumours are associated with significantly increased pretranslational expression of the MEN1 gene. In addition, the single corticotrophinoma showed increased expression compared to normal, as did one of the two TSH-omas. CONCLUSION: Coding mutations of the putative tumour suppressor gene MEN1 are unlikely to contribute to pituitary tumorigenesis in sporadic nonfunctioning, GH-secreting and TSH-secreting adenomas. Changes in pretranslational expression of MEN1 were observed in pituitary tumours, suggesting that changes in the level of MEN1 expression, rather than coding changes, may be of functional importance in influencing sporadic pituitary tumorigenesis.

Adenoma↗
PubMed1999

Association of the large multifunctional proteasome (LMP2) gene with Graves' disease is a result of linkage disequilibrium with the HLA haplotype DRB1*0304-DQB1*02-DQA1*0501.

OBJECTIVE: The large multifunctional proteasome (LMP) molecules are over expressed in thyrocytes, the target cells of Graves' disease, and the LMP genes are found within the MHC class II region. The LMP genes may therefore play a role in susceptibility to Graves' disease. The aim of this this study was to determine whether polymorphisms of the LMP genes, LMP 2 and LMP 7 are in linkage disequilibrium with Graves' disease. DESIGN: Target DNA was amplified using the polymerase chain reaction. The distribution of an Arg-His polymorphism in the LMP 2 gene and a G/T polymorphism in the LMP 7 gene, both of which lead to the presence of an HhaI restriction site, were investigated in a population based case control and family based study in patients with Graves' disease. PATIENTS: We obtained DNA from 306 patients with Graves' disease and 364 control subjects for the population based case-control study. In an independent family based study, DNA was obtained from 129 families including both parents, an affected sibling with Graves' disease and an unaffected sibling. All families, patients and control subjects were white caucasians. MEASUREMENTS: Frequencies of the alleles and genotypes of the LMP 2 and LMP 7 genes were compared between patients and control subjects using the chi2 test. Transmission of alleles from heterozygous parents to affected and unaffected offspring was assessed using the transmission disequilibrium test (TDT). RESULTS: In the case control study, no difference in allele or genotype frequency was seen between patients and control subjects at the LMP7 locus. At the LMP2 locus the R allele and the RH genotype were increased in subjects with Graves' disease when compared with control subjects (R allele: 36.3% vs. 29.5%, pc = 0. 0164; RH genotype: 56.5% vs. 45%, pc = 0.0102). However, the R allele was in linkage disequilibrium with the associated HLA DRB1*0304-DQB1*02-DQA1*0501 haplotype, delta = 0.102. Within the family based study, no preferential allelic transmission was seen from heterozygote parents to offspring at either loci. CONCLUSION: These results show that association of the LMP 2 locus with Graves' disease is due to linkage disequilibrium with the associated HLA haplotype DRB1*0304-DQB1*02-DQA1*0501.

Case-Control Studies↗
PubMed1999

Gender, clinical findings, and serum thyrotropin measurements in the prediction of thyroid neoplasia in 1005 patients presenting with thyroid enlargement and investigated by fine-needle aspiration cytology.

One thousand five euthyroid patients (870 females and 135 males, mean age 47 years), who presented with thyroid enlargement were evaluated by fine-needle aspiration cytology (FNAC) of the thyroid as the first-line investigation. The final cytological or histological diagnosis was determined after surgery (n = 312) or clinical follow-up for a minimum period of 2 years (range 2-14 years, mean 6.7 years). Goiter type was assessed clinically and was classified as diffuse in 147, multinodular in 247, or solitary nodule in 611. The overall sensitivity and specificity of the procedure in the detection of thyroid neoplasia was 88% and 89%, respectively. Males who presented with thyroid enlargement had significantly higher rates of malignancy (p = 0.007) and neoplasia (benign + malignant) (p = 0.002) than females, as did subjects with solitary nodule compared with diffuse or multinodular goiters (malignancy p = 0.001, neoplasia p < 0.001). Subjects with normal thyrotropin (TSH) (>0.4 mU/L) at presentation had a nonsignificantly increased risk of thyroid neoplasia (p = 0.07) and malignancy, in contrast to those with low TSH (<0.4 mU/L). We confirmed FNAC of the thyroid to be an accurate test in the detection of thyroid neoplasia. Gender and goiter type at presentation both contribute significantly to the prediction of the diagnosis of thyroid neoplasia.

Adolescent↗