The incidence of Hashimoto's disease in nodular goitre: the concordance in serological and cytological findings.

OBJECTIVE: To determine the incidence of Hashimoto's disease in nodular goitre and to ascertain the degree of the concordance between serological and cytological findings. METHODS: We retrospectively reviewed data from 188 patients who underwent a fine needle aspiration biopsy of the thyroid for uninodular or multinodular goitre with a documented serological level of antithyroid peroxidase (TPO) antibodies. AntiTPO antibodies were measured by immunochemiluminescent assay (Quest Diagnostics, Madison, NJ, USA). RESULTS: The study cohort consisted of 170 female and 18 male patients with a mean (+/- SD) age of 47.8 +/- 14.9 years. AntiTPO antibodies were positive in 74 (39.36%) of the individuals and negative in 114 (60.63%). The cytodiagnoses were as follows: 5 (2.6%) cancerous, 18 (9.5%) suspicious, 12 (6.3%) inadequate, 92 (48.9%) benign and 61 (32.4%) consistent with chronic lymphocytic thyroiditis (CLT). For further analysis, we excluded all inadequate specimens. Based on the final sample of 176 patients, the sensitivity and specificity of antiTPO antibody test to detect CLT in nodular goitre were estimated to be 76.38% and 94.23% respectively. The prevalence of CLT in nodular goitre based on cytological criteria was (35.46%) compared with (31.97%) goitre based on positive antiTPO titres only. CONCLUSION: There is a high degree of concordance between serological and cytological findings of CLT in people with nodular goitres. The high prevalence of CLT in nodular goitre justifies the use of antiTPO antibodies as part of the workup in this population.

Role of repeated fine-needle aspiration of thyroid nodules with benign cytologic features.

OBJECTIVE: To determine the role of repeated fine-needle aspiration (FNA) biopsy in the evaluation of thyroid nodules initially classified as benign. METHODS: We retrospectively reviewed data on 235 patients with clinically palpable thyroid nodules who underwent a repeated FNA biopsy after an initially benign diagnosis. All the nodules were evaluated and biopsies were obtained by the same endocrinologist. Cytodiagnoses were divided into four major categories: inadequate, benign, suspicious, or malignant. RESULTS: The study cohort consisted of 211 female and 24 male patients with a mean age of 47.1 years. The repeated FNA cytodiagnoses were as follows: 204 (86.8%) remained benign and 19 (8.1%), 11 (4.7%), and 1 (0.4%) became inadequate, suspicious, and malignant, respectively. All patients with benign or inadequate cytologic results on repeated FNA who underwent thyroid surgical resection had benign histologic findings (N = 23). The mean follow-up period between the initial and the last benign FNA cytodiagnosis in the 186 patients without surgical intervention was 1,078 days (2.95 years). Nine of 11 patients with suspicious cytologic results underwent a thyroid surgical procedure, which revealed a benign lesion in 7 and malignant disease in 2 (18%). The other two patients with suspicious cytologic findings had a 13-year clinical follow-up without any clinical evidence of a thyroid malignant lesion. The only patient with malignant cytologic findings on repeated FNA (a 76-year-old woman) refused surgical treatment and was lost to follow-up. CONCLUSION: Although the yield of finding a malignant lesion on repeated FNA biopsy in the follow-up of a presumably benign thyroid nodule may be low, rebiopsy reduces the rate of false-negative diagnosis from an average of 5.2% to <1.3%.

Possible association between high-dose fluconazole and adrenal insufficiency in critically ill patients.

OBJECTIVE: Whereas the antifungal azole ketoconazole interferes with steroidogenesis and can cause adrenal insufficiency, fluconazole in standard doses is thought to not interfere with cortisol production. The objective was to evaluate the effect of high-dose fluconazole therapy on adrenal function in critically ill patients in an intensive care setting. DESIGN: Descriptive case reports. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Two patients, a 77-yr-old man (case 1) with esophageal cancer and a 66-yr-old woman (case 2) with multiple organ failure developed reversible adrenal insufficiency temporally related to the institution and withdrawal of high-dose fluconazole. INTERVENTIONS: Short cosyntropin (adrenocorticotropic hormone; ACTH) stimulation tests. MEASUREMENTS AND MAIN RESULTS: Two days after high-dose fluconazole in case 1, the serum ACTH level was 121 pg/mL (normal range is 9-52 pg/mL), and the peak cortisol after ACTH stimulation was 15.5 microg/dL (normal response is >or=18 microg/dL). Eleven days after discontinuation of fluconazole, the peak cortisol level after ACTH stimulation was 43.4 microg/dL. Twenty-four hours after high-dose fluconazole in case 2, an ACTH stimulation test had a low peak serum cortisol of 16.8 microg/dL. Fluconazole was withdrawn, and 5 days later, the peak stimulated cortisol was 20.6 microg/dL. CONCLUSIONS: Although fluconazole is the therapy of choice for patients in the intensive care setting with Candida infections, two patients with multiple organ failure who received high-dose fluconazole appeared to develop adrenal insufficiency. Although preliminary and anecdotal, these data suggest a need to further investigate the possibility that high-dose fluconazole might cause adrenal insufficiency in already compromised critically ill patients.

Small cell undifferentiated carcinoma of the pancreas. Report of a patient with tumor marker studies.

BACKGROUND: Small cell undifferentiated carcinoma of the pancreas is a rare type of pancreatic neoplasm. METHODS: The authors report the clinical and pathologic aspects of a patient with this malignant lesion and an extensive serologic and immunohistochemical survey of potential ectopically produced hormones or tumor markers. RESULTS: Neuron-specific enolase (NSE) emerged as a tumor marker. CONCLUSIONS: NSE could be valuable in the diagnosis and management of other patients with this rare disease.

Small cell carcinoma of the prostate.

This report details clinical and pathologic aspects of a patient with small cell undifferentiated carcinoma of the prostate and systemic hyperglucagonemia. A panel of potential serologic markers was evaluated in order to document additional evidence of ectopic hormonal production. Immunocytochemical markers were sought in tissue samples from the primary neoplasm and a lung metastasis. Stains were positive for corticotropin (ACTH) and gastrin in both the prostate and in the lung, but no evidence of excess secretion was documented. These findings are consistent with the notion that neuroendocrine activity is common in undifferentiated small cell carcinomas, regardless of their site of origin.

A model clinical program for patients with diabetes and vision impairment.

A program was developed to improve independence, self-esteem, and glycemic control in patients with diabetes and blindness. Twenty-nine individuals with both insulin-dependent and noninsulin-dependent diabetes mellitus entered 12-week programs that included education focusing on diabetes self-management skills for the visually impaired, monitored exercise sessions, and group support. Glycated hemoglobin values fell from 13.0% +/- 0.6% (SEM) to 11.4% +/- 0.5% (P = .001). Exercise tolerance in a 12-minute walk test improved from 0.48 +/- 0.04 to 0.64 +/- 0.05 miles (P = .001). Marked improvements occurred in psychosocial indices, demonstrated through changes in the Rand Mental Health Index from 155 +/- 6 to 174 +/- 5 (P = .0001), the Rosenberg Self-Esteem Scale from 22 +/- 1 to 19 +/- 1 (P = .001), the Zung Depression Scale from 0.50 +/- 0.02 to 0.44 +/- 0.02 (P = .001), and the Diabetes Self-Reliance Test from 60 +/- 3 to 74 +/- 2 (P = .0001).

Immunocytochemistry of the thyroid in surgical and cytologic specimens.

The value of immunocytochemistry in thyroid disease was evaluated in histologic and cytologic material derived from papillary carcinoma (25 cases), follicular carcinoma (nine cases), follicular adenoma (nine cases), Hürthle cell tumor (three cases), medullary carcinoma (two cases), nodular goiter (nine cases), and Hashimoto's thyroiditis (two cases). Thyroglobulin was positive in the follicular cells and/or colloid of all lesions (except medullary carcinoma) and two papillary carcinomas. Vimentin was positive in papillary carcinoma (17 of 25), follicular carcinoma (four of nine), follicular adenoma (four of nine), and nodular goiter (two of nine). Vimentin positivity, which was restricted to follicular cells, was strongest in those cells undergoing oncocytic transformation. Three markers of glandular/acinar secretory differentiation (lactoferrin, lactalbumin, and secretory component) were uniformly negative even in well differentiated follicular structures. In medullary carcinoma, both calcitonin and carcinoembryonic antigen were strongly positive in the parafollicular cells. The antibody panel can definitely identify histogenesis from the thyroid but is of little value in tumor classification. In histologic and cytologic preparations, vimentin positivity does not exclude thyroid follicular cell origin. The method can be successfully applied to richly cellular needle aspirates. This is best achieved with assisted needle aspirations when cellularity is ascertained by on-site microscopic examination of multiple passes.

Primary hyperparathyroidism complicated by multiple myeloma.

A patient with primary hyperparathyroidism and multiple myeloma did not have roentgenographic evidence of either disease, yet there was biochemical evidence for both diseases. Hyperparathyroidism was diagnosed by hypercalcemia and increased parathyroid hormone values. Multiple myeloma was diagnosed by serum gamma-globulin component of 2.74 g/dL with a monoclonal spike and bone marrow plasmacytosis of 31%. The serum IgA level was 2.22 g/dL and the IgG and IgM levels were normal. Serum and urine immunoelectrophoresis showed abnormal IgA and lambda arcs. Computed tomography of the neck localized a parathyroid adenoma that was found and removed at surgery.

Small cell undifferentiated carcinoma of the esophagus. Case report with hormonal studies.

This report details clinical and pathologic aspects of a case of small cell undifferentiated carcinoma of the esophagus. Transmission electron microscopic examination demonstrated neurosecretory granules, and indirect immunoperoxidase stain for adrenocorticotropic hormone (ACTH) was positive. However, the authors detected no abnormal hormone levels in urine or blood. The calculated tumor doubling time was approximately 2 days. The fulminant nature of this carcinoma was also evident from the rapid clinical progression in spite of surgical excision, radiotherapy, and chemotherapy.

Effect of testosterone propionate on protein synthesis by two-dimensional electrophoresis in rat ventral prostate.

Two-dimensional polyacrylamide gel electrophoresis has been used to map the pattern of protein synthesis in rat ventral prostate from both castrate and testosterone treated animals. Proteins were detected by fluorography of 35S-methionine incorporation. In the soluble or cytosol fraction, four major proteins that have molecular weights less than 25,000 and isoelectric points (pI) less then 6.0 and one than has a molecular weight above 30,000 and pI 6.6 are under androgen control. One of these proteins with molecular weight 12,000 and pI 5.4 also appears in the microsomal fraction. Using nonequilibrium pH gradient electrophoresis, soluble proteins of pI greater than 7.0 were investigated. One major protein of 20-25,000 daltons and pI 8.0 appears to be androgen dependent. The ventral prostate from castrate synthesized proteins which are not detectable in androgen stimulated castrates.

Purification of major abundance class of poly(A+)-RNA from rat ventral prostate.

Poly(A+)--RNA from rat ventral prostate was isolated using oligo(dT)-cellulose chromatography. 45% of the total poly(A+)--RNA was a single peak at 10S as demonstrated by centrifugation in a 5-20% sucrose gradient containing 1% SDS. By using complementary DNA probes, it was shown that the 10S RNA contained the major abundance class of poly(A+)--RNA. Denaturing agarose-gel analysis revealed 2 major bands in the 10S poly(A+)--RNA preparation approx. 600 NT and 500 NT (NT = nucleotides) long, resp. Double-stranded 32 P-DNAs complementary to light side and heavy side of the 10S poly(A+)--RNA peak were synthesized and isolated using reverse transcriptase and hydroxyapatite (HAP) chromatography. Approx. 40% of the first strand of the cDNAs were converted to double-stranded structures with a Tm of 88 degrees C. HAP purified double-stranded material was 92% resistant to S1 nuclease. the DNA--DNA reannealing profile of double stranded 32 P-cDNA enriched for the 500 NT band gave a Cot 1/2 of approximately 7 X 10(-4) moles X sec X 1(-1) indicating a complexity for this enriched synthetic gene of 500-600 nucleotide pairs (NTP).

Effect of spironolactone on androgen-dependent proteins in the ventral prostate of the rat.

The effect of spironolactone on five androgen-dependent proteins in the ventral prostate of the rat was investigated by two-dimensional gel electrophoresis. Spironolactone was given to intact male, castrated and androgen-stimulated castrated rats. It has been shown that spironolactone had no influence on the synthesis or accumulation of the androgen-dependent proteins in intact animals. However, spironolactone suppressed the restoration of the major androgen-dependent protein of low molecular weight in castrated rats given testosterone. The mechanism by which spironolactone exerts its anti-androgenic activity was shown to be unrelated to its capacity to inhibit the synthesis or accumulation of the five androgen-dependent proteins studied in this investigation.

In vitro translation of major abundant class poly(A+)-mRNA from rat seminal vesicle.

Total poly (A)-containing messenger RNA [poly(A)-mRNAT] was isolated from seminal vesicles of adult male rats. By preparative 5%-20% linear sucrose gradient centrifugation in 1% SDS, a single peak was seen in the 11S region [poly(A)-mRNA11S]. Poly (A)-mRNAT and poly(A)-mRNA11S were translated in the wheat germ S-30 in vitro translation system. Laemmli-SDS-polyacrylamide slab gel electrophoresis of translation products of poly(A)-mRNAT revealed three major protein bands at approximately 18,500, 15,000, and 14,000 daltons. In vitro translation of poly(A)-mRNA11S across the 11S peak revealed partial purification of the mRNAs for the three predominant proteins. The lower molecular weight part of the 11S peak enriched for the mRNAs coding for the 15,000 and 14,000 dalton polypeptides, and the higher molecular weight side of the peak enriched for the 18,500 dalton mRNA. The highly abundant class of mRNA from rat seminal vesicle can be purified with one sucrose gradient centrifugation.

Isolation and partial purification of the major abundant class rat seminal vesicle poly(A+)-messenger RNA.

Total poly(A(+))-RNA (poly(A(+))-RNA(tot)) was isolated from rat seminal vesicle and its size distribution determined by 70% formamide 5-25% sucrose density analysis. One major peak was resolved in the 10-13 S region and accounted for approximately 35% of the total poly(A(+))-RNA applied. Preparative 1% SDS, 5-20% linear sucrose density gradients also resolved a single major peak in the 11S region (poly(A(+))(11S). Analysis of poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S) under denaturing conditions on 2% agarose gel electrophoresis demonstrated two major components in both poly(A(+))-RNA populations. Size estimations for these components are 620 and 540 NT respectively. (3)H-cDNA was made to both poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S). Back-hybridization of poly(A(+))-RNA(tot) and poly(A(+))-RNA(11S) to their respective (3)H-cDNA revealed a highly abundant class representing 41% and 85% of the sequences in their respective (3)H-cDNA's. The highly abundant class corresponded to 3-5 sequences present in 30,000-50,000 copies/cell. Invitro translation of poly(A(+))-RNA(11S) resulted in two major polypeptides coded for by the 620 NT long and 540 NT long poly(A(+))-RNA respectively.Images

Norepinephrine: hormone and neurotransmitter in man.

To determine whether norepinephrine could subserve a hormonal as well as a neurotransmitter function, norepinephrine was infused for 60 min into each of five normal young men in doses of 0.1, 0.5, 1.0, 2.5, and 5.0 microgram/min. After infusion, the plasma norepinephrine concentration fell with a mean (+/-SD) half-time of 2.4 +/- 0.7 min. The mean (+/-SD) norepinephrine metabolic clearance rate was 3,070 +/- 200 ml/min. The calculated basal plasma norepinephrine production rate was 0.7 microgram/min. The blood pressure and circulating glycerol, acetoacetate, beta-hydroxybutyrate, and glucose (increased) and the heart rate and circulating insulin, lactate, pyruvate, and alanine (decreased) exhibited highly significant parabolic relationships with the steady-state plasma norepinephrine concentrations. However, norepinephrine levels in excess of 1,800 pg/ml were required to produce hemodynamic and/or metabolic effects. Thus, under usual conditions, the biologic actions of norepinephrine can be attributed only to its sympathetic neurotransmitter function. Plasma norepinephrine concentrations do at times exceed 1,800 pg/ml during exercise and during major acute illness. Thus, under conditions of stress, norepinephrine may subserve a hormonal, as well as a neurotransmitter, function.

Resistance to endogenous norepinephrine in Bartter's syndrome: reversion during indomethacin administration.

In five patients with Bartter's syndrome, mean (+/-SE) plasma norepinephrine concentrations increased from 324 +/- 75 pg/ml with the patients in the supine position to 550 +/- 100 pg/ml, 753 +/- 104 pg/ml and 808 +/- 116 pg/ml after 2,5 and 10 minutes, respectively, in the standing position, levels significantly higher than normal. Plasma epinephrine concentrations were indistinguishable from normal. One patient was shown to resistant the pressor (but not the metabolic) effects of intravenously administered norepinephrine prior to treatment with reversion to normal pressor responsiveness during indomethacin administration. Similarly, that patient's exaggerated endogenous norepinephrine response to standing (10 minute plasma value of 1,110 pg/ml) reverted to normal (10 minute value of 462 pg/ml) during indomethacin administration. Thus, patients with Bartter's syndrome exhibit a hyperadrenergic state consisten with resistance to endogenous, as well as exogenous, norepinephrine. Since the metabolic responses to intravenously administered norepinephrine were normal in the patient studied, norepinephrine resistance would appear to be limited to the vasculare system. Reversion of norepinephrine resistance during administration of an inhibitor of prostaglandin synthesis suggests that this hyperadrenergic state is not a primary pathogenetic abnormality in Bartter's syndrome.