The role of frozen section, gender, age, and tumor size in the differentiation of follicular adenoma from carcinoma: a meta-analysis.

BACKGROUND: The purpose of this study was to reanalyze modern trials and use meta-analysis to determine how well frozen section gender, age, and tumor size could differentiate follicular adenoma from follicular carcinoma. METHOD: Inclusion criteria were studies where patients had a permanent pathologic diagnosis of follicular adenoma or follicular carcinoma and underwent frozen section or had clinical features recorded. Data were pooled, and the random effects model of meta-analysis was used. A probability value of less than.05 was considered significant. RESULTS: Nineteen studies were included (n = 3486 patients). Frozen section was evaluated in 11 studies (n = 2204 patients). Frozen section had an 87% sensitivity, a 48% specificity, a 92% and 35% positive and negative predictive value, respectively, an 82% accuracy, an odds ratio of 0.181, a 95% confidence interval (CI) of 0.07 to 0.49, and a probability value of.001. Clinical features were evaluated in 10 studies (n = 1954 patients). Of the patients with follicular carcinoma, 27.5% were male compared with patients with follicular adenoma, of whom 17.7% were male (P <.01; odds ratio, 2.17; CI 1.3-3.6; P =.003). Of the patients with follicular carcinoma, 52.2% were older than 50 years (52.2%) compared with patients with follicular adenoma, of whom 28.5% were older than 50 years (P <.001). Of patients with follicular carcinoma, 36.8% had tumors larger than 3 to 5 cm compared with patients with follicular adenoma, of whom 14.7% had tumors larger than 3 to 5 cm (P <.001; odds ratio, 3.99; CI 1.5-10.8; P =.006). CONCLUSIONS: Meta-analysis suggests that frozen section is not a specific test and cannot be used to confidently rule out follicular carcinoma. Male gender and large tumor size are significantly associated with carcinoma.

Thyroid microcarcinoma: prevalence, prognosis, and management.

OBJECTIVE: To review the usual course of thyroid microcarcinoma (TMC) and the associated prognosis and treatment of affected patients. METHODS: We discuss predisposing factors in the formation of TMC and the modulation of its behavior, diagnostic evaluation, and management options. RESULTS: TMC, generally defined as a well-differentiated thyroid cancer less than or equal to 15 mm in diameter, has an estimated prevalence (based on autopsy studies) of about 5 to 10%. Studies, however, have shown that most of these cancers are smaller than 5 mm in diameter. The high prevalence of TMC in the general population contrasts with the rarity of thyroid cancers of greater size, which constitute less than 1% of malignant neoplasms in the United States. The frequent detection of TMC as a result of routine imaging of the neck for unrelated reasons and as a incidental finding in surgical specimens has raised a question about whether the management of TMC should differ from that for thyroid cancer of appreciable size. The uncertainty about optimal management of TMC is attributable to the small number of long-term follow-up studies as well as the common observation that patients usually have an excellent prognosis. Although in most patients harboring a TMC the cancer remains quiescent and never becomes clinically significant, in some cases TMC can demonstrate an aggressive course. Several variables, such as older age, multifocality, bilateral disease, and extrathyroidal spread at initial assessment, may have some adverse prognostic significance. After a partial surgical removal of the thyroid gland for TMC, the recurrence rate may be as high as 11%. Therefore, a treatment dilemma is caused by the low propensity of TMC for progression to clinically significant disease, yet the potential for recurrence and aggressive behavior in some cases. CONCLUSION: In general, surgical resection of TMC is based on results of fine-needle aspiration biopsy and the rate of growth of the nodule. Aggressive management seems indicated in high-risk patients, particularly older patients, those with a history of radiation exposure, and those with multifocal disease, bilateral disease, or lymph node involvement.

Effect of decreased plasma low-density lipoprotein levels on adrenal and testicular function in man.

OBJECTIVE: The study assessed whether serum LDL cholesterol levels affect adrenal and Leydig cell function in man. DESIGN AND METHODS: A 24-h continuous ACTH infusion was performed in 15 consecutive chronically ill patients. Serum cortisol and DHEA-s were measured at baseline and at 3, 6, 12, 20, and 24 h during the infusion. Fasting serum lipoprotein levels including LDL cholesterol, HDL cholesterol as well as FSH, LH, total and free testosterone concentrations were also measured on the baseline morning samples prior to the infusion. RESULTS: The initial 3 and 6 h percent rise in cortisol values during 24 h ACTH infusion were significantly diminished in patients with LDL-C values < 1.55 mmol/L as compared with patients with higher LDL-C levels (127 +/- 17% (SE) vs. 199 +/- 31% (SE); p < 0.02 and 115 +/- 17% vs. 213 +/- 32%; p < 0.02. However, the 24-h areas of cortisol under the curve were comparable in the 2 groups. Basal and ACTH stimulated DHEA-s levels and percent increases tended to be lower in the low LDL-C group but the differences were not statistically significant. The mean total testosterone was lower in the low LDL-C group (5.30 +/- 1.78 vs. 15.60 +/- 1.95 nmol/L; p < 0.0005). Free testosterone levels were also lower in the low LDL-C group (0.03 +/- 0.009 nmol/L vs. 0.08 +/- 0.01 nmol/L; p < 0.001). Five of six patients with low LDL-cholesterol had low testosterone values, but variable LH levels. CONCLUSIONS: Our results suggest that severe acquired LDL cholesterol insufficiency impairs slightly the initial glucocorticoid response to ACTH stimulation but not the overall cortisol production during sustained ACTH stimulation. It also may contribute to the reduction in testosterone seen in chronically ill patients.

Thyroid function testing in psychiatric illness: Usefulness and limitations.

The assessment of thyroid function in psychiatric patients may be obscured by several effects of the psychiatric condition on both thyroid hormone and TSH levels. Acute psychiatric decompensation may result in elevation in total T(4) and free T(4) index, and less frequently in hypothyroxinemia. In addition, psychiatric illnesses can cause suppressed TSH levels, blunted TSH response to thyrotropin-releasing hormone (TRH) (particularly in depression), and elevated TSH values that may result in diagnostic errors. Even though mechanisms similar to the ones responsible for thyroid function test changes in other nonthyroidal illness could account for some of these abnormalities, other mechanisms involving dysregulation of hypothalamic-pituitary function seem to play an important role. TRH stimulation testing has also been used for the diagnosis and prognosis of some psychiatric disorders. This test, however, appears to have low sensitivity and specificity and little clinical usefulness for this purpose and may be replaced by basal TSH levels determined by highly sensitive assays. In this review, in addition to discussing the usefulness and limitations of thyroid function tests in the setting of a psychiatric condition, we provide a stepwise approach, using sensitive TSH as a first-line test in the assessment of thyroid function in psychiatric patients.

Cardiac systolic and diastolic function at rest and exercise in subclinical hypothyroidism: effect of thyroid hormone therapy.

Cardiac atrial and ventricular parameters were determined by Doppler two-dimensional echocardiography at rest and exercise in 8 patients with subclinical hypothyroidism (SCH) (6 women and 2 men; age range: 28-48 years) before and 3 months after achievement of a euthyroid state with incremental adjustment of L-thyroxine therapy. None of the patients had known heart disease. At 3 months of L-thyroxine therapy, TSH levels decreased from 14.8 +/- 9.4 mIU/L to 3.0 +/- 1.5 mIU/L and FTI increased from 7.1 +/- 1.8 to 8.1 +/- 1.9. The cardiac studies were performed at rest, and during incremental exercise load (50, 100, 150 W workload) on a Quinton exercise bicycle. No significant differences were found between the subclinical hypothyroid and euthyroid states in systolic blood pressure at rest (104.8 +/- 12.3 vs 105 +/- 10.1 mm Hg) and exercise (158 +/- 24.9 vs 158.5 +/- 20.9 mm Hg) or diastolic blood pressure at rest (70 +/- 4.7 vs 69 +/- 5.7 mm Hg) and exercise (86 +/- 11.4 vs 89.2 +/- 7.3 mm Hg). All echocardiographic atrial and ventricular parameters were similar before and during L-thyroxine therapy with the exception of a small but significant change in left ventricular diastolic dimension (4.5 +/- 0.3 vs 4.8 +/- 0.4 cm; p < 0.05). All Doppler parameters were not significantly affected by L-thyroxine therapy with the exception of preejection period at stage III exercise (51 +/- 17 vs 39 +/- 13 msec; p < 0.05). Preejection period at other stages of exercise showed trends toward similar differences between subclinical hypothyroidism and euthyroidism, but the differences were not statistically significant. We conclude that the cardiac structure and function overall remains for practical purposes normal in subclinical hypothyroidism. However, the latter may be responsible for a mild prolongation of the preejection period during exercise and a slightly smaller left ventricular diastolic dimension at rest, changes that may not be of clinical significance in patients without underlying heart disease.

Ipodate therapy in patients with severe destruction-induced thyrotoxicosis.

We describe 4 patients with severe destruction-induced thyrotoxicosis who had a rapid clinical response to oral sodium ipodate (500 mg daily). The underlying thyroid disorders in the patients were postpartum thyroiditis, subacute thyroiditis, silent thyroiditis, and radiation-induced thyroiditis. Ipodate therapy was given for 6 to 10 weeks until restoration of thyroid function to normal. In all patients, an almost complete resolution of symptoms occurred by the third day of ipodate treatment. In the patient with radiation thyroiditis, a daily clinical score of thyrotoxicosis declined within 2 to 3 days. The score remained low as long as the patient was receiving ipodate, but 2 attempts to discontinue ipodate therapy while thyroxine levels were elevated resulted in a rise of the thyrotoxicosis clinical score. This suggests that ipodate therapy, by rapidly reducing triiodothyronine levels through inhibition of the 5' monodeiodination and blockage of the peripheral effects of thyroid hormone, controls severe thyrotoxicosis mediated by destruction and should be considered in this setting in conjunction with beta-adrenergic blockade.

Restriction fragment length polymorphism of the human apo B and apo AII gene regions among type II diabetics.

Levels of plasma low density lipoproteins (LDL) are positively, and high density lipoproteins (HDL) are negatively correlated with an increased risk for atherosclerosis. The frequencies of restriction fragment length polymorphism (RFLP) of the genes for apoB, a major LDL apolipoprotein, and apoAII, a major HDL apolipoprotein, were studied in 45 Tunisian diabetics and an equal number of sex and age matched controls. Southern blot analysis of an EcoR1 apoB polymorphism and an Msp1 apo AII polymorphism indicates that there was no statistically significant difference in the incidence of different genotypes or alleles among diabetics compared to controls.

Effect of L-thyroxine therapy on lipoprotein fractions in overt and subclinical hypothyroidism, with special reference to lipoprotein(a).

The effect of L-thyroxine therapy on lipoprotein fractions was assessed in 15 patients with overt hypothyroidism (14 women and one man aged 45 +/- 3.9 years; thyrotropin [TSH]: mean +/- SEM, 42 +/- 6.5 mIU/L; range, 20.5 to 106.5) and 14 patients with subclinical hypothyroidism (13 women and one man aged 41 +/- 4 years; TSH: mean +/- SEM, 9.1 +/- 1 mIU/L ; range 5.1 to 17.3). Fasting serum lipid levels were measured initially and 4 months after achievement of a euthyroid state with incremental L-thyroxine therapy (TSH: mean +/- SEM, 1.8 +/- 0.4 mIU/L; range, 0.3 to 4.9 for both groups). In the overtly hypothyroid group, restoration of a euthyroid state was associated with a significant reduction in total cholesterol, and apo B. In the subclinically hypothyroid group, there was a significant reduction of only total cholesterol (199.6 +/- 13.2 v 183.4 +/- 11.6 mg/dL) and LDL-C (13.6 +/- 8.4 v 114 +/- 9.25 mg/dL). In contrast, lipoprotein(a) [Lp(a)] was unaffected by the incremental adjustment of L-thyroxine therapy in both groups (overt, 34.3 +/- 8.8 v 35.6 +/- 6.7 mg/dL; subclinical, 23.0 +/- 8.6 v 29.4 +/- 9.5 mg/dL). We conclude that restoration of a euthyroid state in patients with overt hypothyroidism has no significant effect on Lp(a) levels, and confirm that subclinical hypothyroidism is associated with a significant increase in LDL-C, known to have an atherogenic effect.

Assessment of interchangeability of two brands of levothyroxine preparations with a third-generation TSH assay.

PURPOSE: To evaluate, in a prospective fashion, the clinical interchangeability between two brands of levothyroxine, Synthroid (Boots Pharmaceuticals, Inc., Lincolnshire, Illinois) and Levoxine (Daniels Pharmaceuticals, Inc., St. Petersburg, Florida), by using clinical scores of hyperthyroidism and hypothyroidism, free thyroxine index (FTI), sensitive thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone (TRH) stimulation testing. PATIENTS AND METHODS: Twenty-three of the 31 patients with long-standing primary hypothyroidism (6 men, 25 women; age range 30 to 71 years, mean 47.2 +/- 2.2 SEM) were switched from Synthroid to Levoxine (group 1) and the remaining patients from Levoxine to Synthroid (group 2). After switching, each patient continued to receive the same dosage as previously. Clinical scores of hypothyroidism and hyperthyroidism (Billewicz and Crooks scoring systems, respectively), basal FTI, and TRH stimulation test were obtained before and 4 months after the switching. Comparison of the variables before and after switching was performed separately in each subgroup and in the entire group. RESULTS: There was no statistically significant difference in the hypothyroid clinical scores (-40.1 +/- 1.2 versus -39.7 +/- 1.2), the hyperthyroid clinical scores (-19.6 +/- 0.9 versus -19.2 +/- 1.0), FTI (9.6 +/- 0.3 versus 9.6 +/- 0.3), basal TSH levels (1.4 +/- 0.2 versus 1.4 +/- 0.2 mIU/L), or the magnitude of TSH response to TRH (mean delta TSH 9.4 +/- 1.5 versus 9.2 +/- 1.4 mIU/L), whether the patients were receiving Synthroid or Levoxine. CONCLUSIONS: Switching did not result in substantial clinical or laboratory changes in any individual patient. We conclude that the two brands of levothyroxine are clinically interchangeable.

Reduced tissue thyroid hormone levels in fatal illness.

Patients with severe nonthyroidal illnesses (NTIs) frequently have decreased serum concentrations of triiodothyronine (T3) and less often of thyroxine (T4) without clear evidence of hypothyroidism. To determine whether T3 and T4 levels are also reduced in the tissues, we analyzed autopsy samples from 12 patients dying of NTI and 10 previously healthy individuals dying suddenly from trauma. Mean serum T3, T4, and free T4 index values were lower by 79%, 71%, and 49%, respectively, in the NTI group than in controls, but serum thyrotropin (TSH) values did not differ significantly. Mean T3 concentrations in cerebral cortex, hypothalamus, pituitary, liver, kidney, and lung were lower in the NTI group than in controls by 43% to 76%, but mean values in heart and skeletal muscle did not differ significantly between the groups. The mean liver T4 concentration was 66% lower in the NTI group, but mean T4 concentrations in the cerebral cortex were similar in the two groups. These results indicate that many tissues may be deficient in thyroid hormones in patients with fatal NTI, although the severity of the reduction in thyroid hormone concentrations may vary from one organ to another.

Concomitant euthyroid Graves' ophthalmopathy and isolated ocular myasthenia gravis.

A 44 year old diabetic woman presented with diplopia and bilateral ptosis and mild exophthalmos. The patient was clinically euthyroid, the baseline thyroid function tests were normal, but the thyroid stimulating hormone response to thyrotrophin releasing hormone was flat. Computed tomographic scan and magnetic resonance imaging of the orbits showed left medial and inferior rectus muscle thickening, more prominent on the left side, consistent with Graves' disease. The tensilon stimulation test resulted in resolution of the ptosis and partial improvement of the ophthalmoplegia. The single fibre electromyography was consistent with a defect in neuromuscular transmission. However, forced duction test was normal and anti-acetylcholine receptor antibodies were undetectable. Significant improvement of the extraocular muscle function and resolution of the right ptosis had resulted from anticholinesterase therapy. These findings and the clinical response to therapy were consistent with concomitant euthyroid Graves' ophthalmopathy and ocular myasthenia gravis. Coexistent isolated ocular myasthenia gravis and Graves' ophthalmopathy is rare and should be considered in patients with findings of ocular myasthenia and extraocular muscle dysfunction.

Lipoprotein and apolipoprotein levels in subclinical hypothyroidism. Effect of levothyroxine therapy.

To assess whether subclinical hypothyroidism is associated with changes in lipoprotein fractions, 13 patients maintained in a stable state of subclinical hypothyroidism for at least 3 months were studied prior to and 2 and 4 months following restoration of a euthyroid state with incremental levothyroxine sodium therapy. Thyrotropin levels ( +/- SEM) had decreased from 16.6 +/- 3.2 mU/L to 3.1 +/- 0.7 mU/L and 3.2 +/- 0.7 mU/L at 2 months and 4 months. At 2 months, levothyroxine treatment led to a decrease in levels of total cholesterol from 5.5 +/- 0.3 mmol/L (213 +/- 12 mg/dL) to 4.8 +/- 0.3 mmol/L (186 +/- 12 mg/dL), in low-density lipoprotein cholesterol (LDL-C) from 3.7 +/- 0.3 mmol/L (143 +/- 12 mg/dL) to 2.9 +/- 0.3 mmol/L (112 +/- 12 mg/dL), and in apolipoprotein B from 91 +/- 8 mg/dL to 74 +/- 7 mg/dL. At 4 months, levels of LDL-C and apolipoprotein B remained significantly lower than pretreatment values (2.9 +/- 0.2 mmol/L [112 +/- 8 mg/dL] and 75 +/- 6 mg/dL, respectively). While high-density lipoprotein cholesterol (HDL-C), HDL3-C, and apolipoprotein A-I were not significantly affected by levothyroxine therapy, there was a slight trend of increase in HDL2-C during levothyroxine substitution. There was also a tendency for a decrease in triglyceride levels from 1.3 +/- 0.2 mmol/L (115 +/- 18 mg/dL) to 0.9 +/- 0.1 mmol/L (80 +/- 9 mg/dL) at 4 months of levothyroxine therapy. Levels of HDL-C tended to decrease from 4.8 +/- 0.4 mmol/L (186 +/- 15 mg/dL) to 4.5 +/- 0.5 mmol/L (174 +/- 19 mg/dL) at 2 months and to 3.9 +/- 0.4 mmol/L (151 +/- 15 mg/dL) at 4 months. The LDL-C/HDL-C ratio also decreased from 3.3 +/- 0.3 mmol/L (128 +/- 12 mg/dL) to 2.9 +/- 0.5 mmol/L (112 +/- 19 mg/dL) and 2.5 +/- 0.3 mmol/L (97 +/- 12 mg/dL) at 2 months and 4 months, respectively. These results suggest that long-term levothyroxine therapy in patients with subclinical hypothyroidism is associated with a decrease in LDL-C and apolipoprotein B levels that are reflected in a trend of decreases in cholesterol/HDL-C and LDL-C/HDL-C ratios known to have a relationship with coronary artery disease.

Value of sensitive thyrotropin measurement in ambulatory and hospitalized patients.

To compare the frequency and causes of abnormal thyrotropin (TSH) levels in ambulatory and hospitalized patients and to assess the specificity and sensitivity of suppressed TSH for the diagnosis of hyperthyroidism in these two settings, analysis of thyroid function tests including sensitive TSH measurement was performed on 715 consecutive patients who had a thyroid panel performed in one clinical laboratory. Suppressed TSH (less than 0.3 mU/L) and elevated TSH (greater than 5.5 mU/L) were found in 35 (8.5%) and 28 (6.5%) of the 411 regular ward inpatients. The prevalence of suppressed TSH was significantly higher than that of high TSH among the 267 ambulatory patients (11.6% vs 5.6%, p less than 0.03). A total of 37 severely ill ICU patients had a significantly higher prevalence of both suppressed and elevated TSH (16% and 22% respectively) than regular ward inpatients and ambulatory patients. Hyperthyroidism and exogenous thyroid hormone administration were responsible for suppressed TSH in 65% of ambulatory patients and in 34% of regular ward and ICU patients. In contrast nonthyroidal illness was implicated in 36% of hospitalized patients and in 6% of ambulatory patients. The sensitivity and specificity of suppressed TSH for the diagnosis of hyperthyroidism was 90% and 91% for ambulatory patients and 100% and 91% for hospitalized patients respectively. The predictive value of suppressed TSH for hyperthyroidism was higher in outpatients (26%) than in hospitalized patients (7%). After patients with known causes for suppressed TSH other than thyroid disease had been excluded, the corrected predictive values of suppressed TSH for hyperthyroidism were 57% in outpatients and 21% in hospitalized patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal nonthyroidal illness may impair nocturnal thyrotropin levels.

PURPOSE: This study was undertaken to assess whether circadian variation of thyrotropin (TSH) is affected by the severity of a nonthyroidal illness. PATIENTS AND METHODS: On the second day of admission to a medical intensive care unit, 20 consecutive patients with the major diagnosis of acute respiratory failure underwent TSH measurements at 8 A.M., 9 P.M., 11 P.M., and 1 A.M., with two sensitive assays. RESULTS: Six patients died, five of whom had hypothyroxinemia (thyroxine [T4] less than 5.5 micrograms/dL) (83%) on the day of the study, whereas only three of the 14 survivors had low T4 (21%; p less than 0.05). Baseline 8 A.M. TSH measured with the two assays was similar in both groups and there was a progressive increase in TSH in survivors and a decrease in nonsurvivors at 9 P.M. and 11 P.M. However, the difference at these time points was not statistically significant. At 1 A.M., TSH levels were significantly lower among nonsurvivors (0.75 +/- 0.34 microU/mL with assay 1, and 0.7 +/- 0.4 microU/mL with assay 2) than in survivors (2.3 +/- 0.46 microU/mL with assay 1, and 2 +/- 0.5 microU/mL with assay 2; p less than 0.005; Wilcoxon test). Five of the nonsurvivors and none of the survivors had a suppressed 1 A.M. TSH level (p less than 0.001), suggesting a good correlation between suppressed 1 A.M. TSH and mortality. After exclusion of patients receiving drugs known to affect TSH levels (two nonsurvivors and four survivors), the same dissociation in TSH changes was observed, and significantly lower 1 A.M. TSH levels were observed in nonsurvivors than in survivors (0.13 +/- 0.08 microU/mL versus 2.7 +/- 0.6 microU/mL with assay 1; p less than 0.01). Cortisol levels were significantly higher only at 8 A.M. in nonsurvivors whether patients receiving drugs were included in the analysis (41.6 +/- 3.2 versus 28.4 +/- 2.7 micrograms/dL; p less than 0.01) or not (45.3 +/- 4.6 versus 30.5 +/- 3.6 micrograms/dL; p less than 0.01). At other times, cortisol levels were similar in both groups. The 24-hour TSH areas under the curve were also lower in nonsurvivors than in survivors whether patients receiving drugs known to affect TSH levels were included or not. However, cortisol areas under the curve were similar in both groups. CONCLUSION: It is concluded that fatal illness is associated with a suppression of the late night TSH surge.

Diabetic diarrhea. Pathophysiology, diagnosis, and management.

Idiopathic diarrhea is a common complication of diabetes mellitus. It occurs frequently, but not exclusively, in patients with poorly controlled insulin-dependent diabetes who also have evidence of diabetic peripheral and autonomic neuropathy. Associated steatorrhea is common and does not necessarily imply a concomitant gastrointestinal disease. The diarrhea is often intermittent; it may alternate with periods of normal bowel movements, or with constipation. It is typically painless, and occurs during the day as well as at night and may be associated with fecal incontinence. Multiple pathogenic mechanisms have been implicated, autonomic neuropathy, bacterial overgrowth, and pancreatic exocrine insufficiency being the most important underlying aberrations. However, diabetic diarrhea does not have a uniform and unequivocal pathogenesis. The diagnosis depends on a judicious clinical assessment accompanied by a stepwise laboratory evaluation, which allows the differentiation idiopathic diabetic diarrhea from the many other causes of diarrhea that can occur in diabetic and nondiabetic patients. The management can be difficult but many therapies, including antibiotics to eradicate bacterial overgrowth, as well as antidiarrheal agents, oral and topical clonidine, and somatostatin analogues may be effective in controlling diabetic diarrhea.

Recurrent transient thyrotoxicosis in multinodular goitre.

A patient initially presented with an autonomously functioning right thyroid nodule and transient hyperthyroidism which lasted for a few months. Several months after resolution of thyrotoxicosis, the patient had a recurrent episode of hyperthyroidism and was found to have a left hot nodule. The right hyperfunctioning nodule had become cold on scintigraphy, and its aspiration revealed haemorrhagic fluid suggesting haemorrhagic infarction as the mechanism of resolution of the first episode of hyperthyroidism. Again following resolution of the second episode of hyperthyroidism, the left hot nodule also became hypofunctioning on scintigraphy indicating that the spontaneous restoration to euthyroidism was secondary to infarction. Recurrent hyperthyroidism and resolution due to nodular infarction in a patient with a nodular goitre may mimic the more common causes of transient thyrotoxicosis and should be considered in the differential diagnosis of goitrous hyperthyroidism.

Hypoglycemia associated with renal failure.

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.

Radionuclide thyroid studies: analysis of use and correlation with physical findings.

We assessed all thyroid radionuclide studies done at a single institution during one year and evaluated the indication for ordering each study as well as the concordance of study results with those of physical examination. We found that thyroid radionuclide imaging was overused, with at most 66% of scans being indicated (using the most generous classification of a proposed rating for indications). Radioactive iodine uptake measurement done without scanning was probably underused. Concordance between the results of physical examination and scanning was reflected by an overall agreement rate of 51%; agreement between results of scanning and physical examination beyond what might be expected by chance alone was reflected by a kappa value of .34. Concordance was strongest for diffuse goiters and weakest for normal findings.

Fasting and postabsorptive hepatic glucose and insulin metabolism in hyperthyroidism.

The effect of thyroid hormone excess on hepatic glucose balances and fractional hepatic extraction of insulin and glucagon was examined in six conscious dogs with catheters in the portal vein, hepatic vein, and femoral artery and Doppler flow probes on the portal vein and hepatic artery. An oral glucose tolerance test was performed before and after the animals were made hyperthyroid by intramuscular thyroxine administration (100 micrograms.kg-1.day-1) for 10 days. In the basal state and after oral glucose, insulin and glucagon levels in the three vessels and the basal fractional hepatic extraction of insulin and glucagon were not significantly modified by thyroid hormone. These results suggest that in short-term thyrotoxicosis insulin secretion is not impaired, and the rise in fasting plasma glucose and increased hepatic glucose production could reflect hepatic insulin resistance, increased availability of precursors for gluconeogenesis, or increased glycogenolysis. Hyperthyroidism significantly increased basal flows in the portal vein (14.7 +/- 0.6 vs. 12.9 +/- 0.5 ml.kg-1.min-1), the hepatic artery (4.8 +/- 0.3 vs. 3.9 +/- 0.2 ml.kg-1.min-1) and vein (19.6 +/- 0.7 vs. 16.9 +/- 0.4 ml.kg-1.min-1), the fasting plasma glucose concentration (104 +/- 3 vs. 92 +/- 2 mg/dl), and basal hepatic glucose output (2.1 +/- 0.2 vs. 1.5 +/- 0.2 mg.kg-1.min-1). It did not alter the nonhepatic splanchnic uptake of glucose, the percent of orally administered glucose that appeared in the portal vein (47 +/- 2 vs. 45 +/- 11%), the percent of hepatic uptake of glucose (59 +/- 11 vs. 74 +/- 22%), or the shape of the glucose tolerance test.