No calcitonin change in a person taking dulaglutide diagnosed with pre-existing medullary thyroid cancer.

BACKGROUND: Glucagon-like peptide-1 receptor agonists, such as dulaglutide, exenatide and liraglutide, are approved to treat Type 2 diabetes mellitus. Although these drugs provide substantial glycaemic control, studies in rodents have prompted concerns about the development of medullary thyroid carcinoma. These data are reflected in the US package insert, with boxed warnings and product labelling noting the occurrence of these tumours after clinically relevant exposures in rodents, and contraindicating glucagon-like peptide-1 receptor agonist use in people with a personal or family history of medullary thyroid carcinoma, or in people with multiple endocrine neoplasia type 2. However, there are substantial differences between rodent and human responses to glucagon-like peptide-1 receptor agonists. This report presents the case of a woman with pre-existing medullary thyroid carcinoma who exhibited no significant changes in serum calcitonin levels despite treatment with dulaglutide 2.0 mg for 6 months in the Assessment of Weekly AdministRation of LY2189265 [dulaglutide] in Diabetes-5 clinical study (NCT00734474). CASE REPORT: Elevated serum calcitonin was noted in a 56-year-old woman with Type 2 diabetes mellitus at the 6-month discontinuation visit in a study of long-term dulaglutide therapy. Retroactive assessment of serum collected before study treatment yielded an elevated calcitonin level. At 3 months post-study, calcitonin level remained elevated; ultrasonography revealed multiple bilateral thyroid nodules. Eventually, medullary thyroid carcinoma was diagnosed; the woman was heterozygous positive for a germline RET proto-oncogene mutation. CONCLUSION: The tumour was not considered stimulated by dulaglutide therapy because calcitonin remained stable throughout.

Safety and activity of vandetanib in combination with everolimus in patients with advanced solid tumors: a phase I study.

BACKGROUND: Preclinical studies suggest that combining vandetanib (VAN), a multi-tyrosine kinase inhibitor of rearranged during transfection (RET) proto-oncogene, vascular endothelial growth factor receptor (VEGFR), and epidermal growth factor receptor (EGFR), with everolimus (EV), a mammalian target of rapamycin (mTOR) inhibitor, may improve antitumor activity. We determined the safety, maximum tolerated dose (MTD), recommended phase II dose (RP2D), and dose-limiting toxicities (DLTs) of VAN + EV in patients with advanced solid cancers and the effect of combination therapy on cancer cell proliferation and intracellular pathways. PATIENTS AND METHODS: Patients with refractory solid tumors were enrolled in a phase I dose-escalation trial testing VAN (100-300 mg orally daily) + EV (2.5-10 mg orally daily). Objective responses were evaluated using RECIST v1.1. RET mutant cancer cell lines were used in cell-based studies. RESULTS: Among 80 patients enrolled, 72 (90%) patients were evaluable: 7 achieved partial response (PR) (10%) and 37 had stable disease (SD) (51%; duration range: 1-27 cycles). Clinical benefit (SD or PR ≥ 6 months) was observed in 26 evaluable patients [36%, 95% confidence intervals (CI) (25% to 49%)]. In 80 patients, median overall survival (OS) was 10.5 months [95% CI (8.5-16.1)] and median progression-free survival (PFS) 4.1 months [95% CI (3.4-7.3)]. Six patients (7.5%) experienced DLTs and 20 (25%) required dose modifications. VAN + EV was safe, with fatigue, rash, diarrhea, and mucositis being the most common toxicities. In cell-based studies, combination therapy was superior to monotherapy at inhibiting cancer cell proliferation and intracellular signaling. CONCLUSIONS: The MTDs and RP2Ds of VAN + EV are 300 mg and 10 mg, respectively. VAN + EV combination is safe and active in refractory solid tumors. Further investigation is warranted in RET pathway aberrant tumors.

Organ-specific effects of tiratricol: a thyroid hormone analog with hepatic, not pituitary, superagonist effects.

Tiratricol has been used to suppress pituitary TSH secretion, with reported attenuation of extrapituitary thyromimetic effects. A randomized, double-blind trial was performed to define precisely the tissue-specific thyromimetic actions of tiratricol. Ten athyreotic patients, treated for thyroid carcinoma, were randomly assigned to receive L-T4 sodium 0.7 micrograms/kg daily and either tiratricol 10 micrograms/kg or placebo twice daily. The daily dose of L-T4 was increased by 25-50 micrograms increments until the TRH-stimulated TSH level was less than 0.1 mU/L. After measurement of biochemical and physiological parameters of thyroid hormone actions, patients crossed treatment groups. Patients required 46% less L-T4 to achieve equivalent TSH suppression when taking tiratricol. Hepatic effects were enhanced by tiratricol administration, with significant increases in sex hormone binding globulin and ferritin concentrations, 14% and 37%, respectively. Levels of serum cholesterol, LDL cholesterol, and apolipoprotein B were reduced by 7%, 10%, and 13%, respectively, during tiratricol therapy. Triglyceride levels also declined, but there were no changes of high density lipoprotein cholesterol or apolipoproteins AI and AII. Resting metabolic rate, body weight, urea nitrogen excretion, and symptoms did not differ between the two treatment regimens. Cardiovascular function, as reflected by mean arterial pressure and pulse wave arrival time, was not different during tiratricol therapy. Skeletal metabolic activity was affected by tiratricol, with marked elevation of osteocalcin without significant change in serum calcium, PTH, and urinary calcium and hydroxyproline excretion. Tiratricol has increased hepatic and skeletal actions of potential therapeutic value, but does not have enhanced thyromimetic activity specific to the pituitary gland.

Prognosis and treatment of brain metastases in thyroid carcinoma.

We analyzed 47 cases of brain metastases from thyroid cancer seen at 1 institution over 5 decades. Brain metastases were a primary clinical feature at initial presentation in 15% of the cases, were identified during the subsequent course of the disease in 68%, and were only discovered at autopsy in 23%. The primary thyroid tumor was differentiated cancer in 68%, anaplastic cancer in 23%, and medullary cancer in 9%. Patients were typically older, with frequent evidence of aggressive disease and distant metastases at initial cancer diagnosis. Once brain metastases were diagnosed, disease-specific mortality was 78%, with a median product-limit survival of 4.7 months (67% and 12.4 months, respectively, for those with differentiated cancer). Resection of one or more foci of brain metastases significantly improved survival. The median disease-specific survival from diagnosis of brain metastases was 16.7 months for patients who underwent local excision of one or more brain metastases, compared with 3.4 months for those who did not (P < 0.05), independent of the presence of multifocal brain lesions. Recombinant human TSH safely stimulated radioiodine uptake for treatment of brain metastases in 1 patient. However, no evidence of survival benefit was found from radioiodine therapy, external beam radiotherapy, or chemotherapy. In summary, brain metastases from thyroid carcinoma are an extremely poor prognostic sign. Although selection bias and other unidentified factors inherent to retrospective analysis limit this conclusion, surgical resection of brain metastases may be associated with prolonged survival in differentiated carcinoma.

Clinical utility of posttreatment radioiodine scans in the management of patients with thyroid carcinoma.

A retrospective comparison was performed of whole body scans obtained before and after 143 131I treatments in 93 patients with thyroid carcinoma. Pretreatment scans were performed with 74-185 megabecquerel 131I, and posttreatment scans were performed 5-12 days after dosing with 1.1-7.4 GBq. In 38 (27%) treatment cycles, the results of posttreatment and pretreatment scans differed. Only 14 (10%) posttreatment scans detected new locations of metastatic disease. Seventeen posttreatment scans demonstrated metastatic locations that were already known from previous studies but not seen on the pretreatment scan. Among parameters evaluated (including demographic and histological characteristics), only the combination of age at diagnosis less than 45 yr and history of previous 131I therapy contributed to the likelihood of a new finding on posttreatment scan (relative risk, 3.8). Five of the 14 new posttreatment scan findings were subsequently corroborated by other radiographic studies or thyroglobulin elevations, all in patients with extrathyroidal extension of the primary tumor. Seven (5%) posttreatment scans were unable to detect a focus of uptake seen on the corresponding pretreatment scan. In conclusion, posttreatment scans were most likely to reveal clinically important new information in young patients who had previously received 131I therapy. In older patients and those without previous 131I therapy, posttreatment scans rarely yielded new information that would potentially alter the patient's prognosis.

Augmented hepatic and skeletal thyromimetic effects of tiratricol in comparison with levothyroxine.

A thyroid hormone analog with organ-selective effects could have therapeutic application for disorders such as hyperlipidemia and osteoporosis. We performed a randomized clinical trial to determine the specific thyromimetic effects of tiratricol. Twenty-four athyreotic patients underwent detailed metabolic and physiological evaluation after a 2-month baseline period, taking TSH-suppressive doses of L-T4. They were then randomized to blinded treatment with either tiratricol (24 micrograms/kg twice daily) or L-T4 (1.9 micrograms/kg daily). The dose of hormone was increased until the TSH level was less than 0.1 mU/L, and the metabolic and physiological testing was repeated. Comparing the change from baseline to the study drug periods, when serum TSH levels were equivalently suppressed, there were no significant differences between the two groups in resting metabolic rate, weight, urea nitrogen excretion, or symptom score. Plasma total and low density lipoprotein cholesterol levels declined 13 +/- 4% and 23 +/- 6% in the tiratricol group compared with 2 +/- 2% and 5 +/- 3% in the L-T4 group (P = 0.015 and P = 0.0066, respectively). Serum sex hormone-binding globulin levels increased 55 +/- 13% with tiratricol compared with a 1.7 +/- 4% decline with L-T4 (P = 0.0006), indicating an augmented hepatic response to tiratricol. Skeletal metabolic activity was enhanced, with increased levels of serum osteocalcin and urinary excretion of calcium and pyridinium cross-links. Tiratricol and L-T4 had comparable effects on cardiovascular function. Tiratricol has distinct augmented hepatic and skeletal thyromimetic actions of potential therapeutic value.

A consensus report of the role of serum thyroglobulin as a monitoring method for low-risk patients with papillary thyroid carcinoma.

Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.

A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.

Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence.

Percutaneous transluminal coronary angioplasty in hypothyroidism.

PURPOSE: To determine the risks of percutaneous transluminal coronary angioplasty (PTCA) in hypothyroid individuals. PATIENTS AND METHODS: In a retrospective cohort study, 13 patients with primary hypothyroidism were identified among 382 consecutive PTCA cases in 1987. Twenty-two euthyroid PTCA control subjects and 13 hypothyroid patients who underwent coronary artery bypass surgery (CAB) were identified for comparison. RESULTS: Hypothyroid and euthyroid PTCA patients had similar mean ages, numbers of prior and recent acute myocardial infarctions, diseased coronary arteries, coronary arteries dilated, and serum cholesterol levels. There were no significant differences in procedure-related mortality (0% versus 0%); coronary artery dissection (23% versus 23%); reocclusion (8% versus 5%); bradycardia (0% versus 0%); heart failure (0% versus 5%); hypotension (31% versus 27%); myocardial infarction (8% versus 0%); gastrointestinal dysfunction (0% versus 0%); neuropsychiatric disturbance (15% versus 9%); hyponatremia (23% versus 23%); hypothermia (0% versus 0%); or fever (15% versus 5%). Hematoma formation tended to be more frequent in the hypothyroid group (38% versus 18%, p = 0.18). Similar results were obtained when the subgroup of more severely hypothyroid patients (thyrotropin level more than 20 mU/L, n = 7) was examined. Compared to hypothyroid CAB patients, hypothyroid PTCA patients had less incidence of heart failure (0% versus 31%, p less than 0.025); neuropsychiatric disturbance (15% versus 54%, p less than 0.025); hyponatremia (23% versus 62%, p less than 0.05); gastrointestinal dysfunction (0% versus 23%, p less than 0.025); and fever (15% versus 62%, p less than 0.001). CONCLUSION: PTCA can be performed in hypothyroid patients without increased mortality or major morbidity, and when appropriate, may be preferred to bypass surgery for coronary revascularization in patients intolerant of full thyroid hormone replacement.

Clinical and socioeconomic predispositions to complicated thyrotoxicosis: a predictable and preventable syndrome?

PURPOSE: To identify the clinical, demographic, and hormonal features that characterize and place patients at greater risk for complicated thyrotoxicosis. PATIENTS AND METHODS: Fifty-nine patients with documented thyrotoxicosis complicated by cardiovascular, neuropsychiatric, gastrointestinal, or thermoregulatory dysfunction, were retrospectively identified among 498,000 hospital admissions between 1979 and 1992. Clinical, demographic, and hormonal information were obtained from these charts, as well as from the charts of 118 randomly selected thyrotoxic outpatients. RESULTS: Age distribution of complicated thyrotoxicosis patients was bimodal, with a median of 41 years. Forty-nine percent of patients had been previously diagnosed with thyrotoxicosis, but most had been noncompliant with prescribed medication. Cardiovascular complications were among the primary causes for admission in 46% of patients, followed by neuropsychiatric indications in 42%, fever in 34%, and gastrointestinal dysfunction in 17%. Only 8% had primary involvement of > 2 organ systems. There was high correlation between organ systems with pre-existing dysfunction and those with a complication of thyrotoxicosis (P < 0.0001). Compared to uncomplicated controls, patients with complicated thyrotoxicosis were more likely to be uninsured or covered by Medicaid (OR, 2.64; 95% CI 1.78 to 3.91); to be < 30 or > 50 years old (OR, 1.93; 95% CI 1.23 to 3.03); and to have serum T4 concentrations greater than twice the upper limit of normal (OR, 1.67; 95% CI, 1.15 to 2.44). CONCLUSIONS: Certain thyrotoxic patients are at greater risk for developing complications. By addressing the medical needs of these patients, it may be possible to reduce the likelihood of complications requiring hospitalization.

Sucralfate causes malabsorption of L-thyroxine.

PURPOSE: To determine if sucralfate causes malabsorption of L-thyroxine. PATIENTS AND METHODS: Five healthy volunteers ingested L-thyroxine, 1,000 micrograms, administered orally (1) without sucralfate, (2) with sucralfate, 1 g, and (3) 8 hours after sucralfate, 2 g. The amount of L-thyroxine absorbed was calculated from the peak increase in serum T4 levels within 6 hours of hormone ingestion multiplied by the volume of distribution for the hormone. RESULTS: Peak absorption of L-thyroxine in the absence of sucralfate was 796 micrograms (95% confidence interval (CI): 515-1,074 micrograms). Coadministration of sucralfate, 1 g, with L-thyroxine reduced thyroid hormone absorption to 225 micrograms (95% CI: 151-299 micrograms) (P = 0.0029 compared with control). Peak hormone absorption was delayed 2 hours by simultaneous sucralfate ingestion. Separation of administered L-thyroxine and sucralfate doses by 8 hours returned hormone absorption to control values. Maximum T3 levels did not differ, regardless of drug regimen, but suppression of thyroid-stimulating hormone (TSH) by L-thyroxine was reduced by coadministration of sucralfate. CONCLUSIONS: Sucralfate causes malabsorption of L-thyroxine, presumably by intraluminal binding of hormone.

Optimal treatment strategy in patients with papillary thyroid cancer: a decision analysis.

BACKGROUND: The management of patients with papillary thyroid carcinoma (PTC) remains controversial. We used decision analysis to identify the optimal treatment strategy for patients with PTC, stratified by risk-group classification. METHODS: We designed a Markov model to compare thyroid lobectomy and total thyroidectomy (with adjuvant radioiodine therapy) in low- and high-risk patients with PTC. Morbidity, recurrence, and mortality estimates were obtained from the literature. Outcomes were quality-adjusted by using health state preferences. RESULTS: In low-risk patients, lobectomy and total thyroidectomy resulted in 31.7 and 32.9 quality-adjusted life years (QALYs). Total thyroidectomy was the optimal strategy as long as the relative risk of recurrence after lobectomy was greater than 1.3. Lobectomy became the preferred strategy if subjects were willing to give up 1.5 years of life to avoid thyroid hormone dependency and a remote risk of radioiodine-induced malignancy. In high-risk patients, lobectomy and total thyroidectomy resulted in 11.2 and 16.5 QALYs. Model results were robust to varying the permanent complication rates of initial or completion thyroidectomy, the efficacy of adjuvant radioiodine therapy, and the impact of complications and cancer recurrence on quality of life, irrespective of risk-group classification. CONCLUSIONS: Total thyroidectomy maximized quality-adjusted life expectancy in low- and high-risk patients with PTC.

Unknown primary cancer presenting as an adrenal mass: frequency and implications for diagnostic evaluation of adrenal incidentalomas.

BACKGROUND: Fine-needle aspiration biopsy to identify adrenal metastasis from an occult primary malignancy has been recommended as part of the evaluation of the patient who presents with an incidentally discovered adrenal mass. This recommendation was assessed by examining the frequency of adrenal involvement in patients with suspected unknown primary cancer. METHODS: Data from 1715 patients referred for evaluation of suspected unknown primary cancer were retrospectively reviewed. RESULTS: Of 1639 patients found to have cancer, the adrenal gland was identified as a site of involvement at presentation in 95 (5.8%). Involvement was limited to the adrenal gland in 4 patients (0.2%). All 4 patients had large (> or = 6 cm) adrenal tumors, 3 of 4 had bilateral involvement, and all had symptoms that otherwise mandated evaluation for an occult malignancy; none had a true adrenal incidentaloma. CONCLUSIONS: Although cancer of an unknown primary site occasionally involves the adrenal gland, metastatic cancer presenting as a true adrenal incidentaloma is extremely rare. Therefore, in the absence of a history of prior malignancy or symptoms, physical examination findings, radiographic findings, or laboratory findings suggestive of an occult malignancy, we do not recommend fine-needle aspiration biopsy as part of the diagnostic evaluation of the patient who presents with a unilateral adrenal mass.

Adenocarcinoma of the salivary gland metastatic to the pituitary gland: case report.

OBJECTIVE AND IMPORTANCE: A case of metastasis to the pituitary gland from a ductal adenocarcinoma of the salivary gland is presented. Metastasis to this site is rare, and a salivary gland source has never previously been described. CLINICAL PRESENTATION: This patient presented with hypopituitarism, including diabetes insipidus. INTERVENTION: A craniotomy was performed to alleviate visual loss. The histological features of the sellar tumor were identical to those of a tumor removed from the parotid gland 18 months earlier. CONCLUSION: Although intrasellar tumors originating from embryonic rests of salivary gland tissue have been reported, metastasis from a malignant neoplasm arising within a true salivary gland is also possible and should not be excluded from consideration for patients in whom a salivary gland-like tumor is discovered in the sella turcica.

Effects of pharmacological fiber supplements on levothyroxine absorption.

To determine the effect of pharmacological fiber supplements, we measured levothyroxine (LT4) absorption without and with simultaneous ingestion of either calcium polycarbophil or psyllium hydrophilic mucilloid. Serum thyroxine (T4) levels in 8 volunteers were measured following ingestion of 600 microg of LT4 on 3 separate occasions at 4-week intervals: (1) LT4 alone; (2) LT4 together with 1000 mg polycarbophil; and (3) LT4 together with 3.4 g psyllium. The amount of absorbed LT4 was calculated as the incremental rise in serum T4 level during the first 6 hours multiplied by the volume of distribution for the hormone, and expressed as a percentage of the dose administered. Absorption of LT4 alone averaged 89% (95% confidence interval [CI]: 75%-104%), occurring at a median of 180 minutes. After simultaneous ingestion of calcium polycarbophil, LT4 absorption was 86% (95% CI: 74%-97%), occurring at 180 minutes. With simultaneous ingestion of psyllium and LT4, the absorption was 80% (95% CI: 64%-95%), occurring at 240 minutes. In summary, neither calcium polycarbophil nor psyllium hydrophilic mucilloid are likely to cause malabsorption of LT4 that could be detected by these methods.

Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: results from the National Thyroid Cancer Treatment Cooperative Registry.

The ideal therapy for differentiated thyroid cancer is uncertain. Although thyroid hormone treatment is pivotal, the degree of thyrotropin (TSH) suppression that is required to prevent recurrences has not been studied in detail. We have examined the relation of TSH suppression to baseline disease characteristics and to the likelihood of disease progression in a cohort of thyroid cancer patients who have been followed in a multicenter thyroid cancer registry that was established in 1986. The present study describes 617 patients with papillary and 66 patients with follicular thyroid cancer followed annually for a median of 4.5 years (range 1-8.6 years). Cancer staging was assessed using a staging scheme developed and validated by the registry. Cancer status was defined as no residual disease; progressive disease at any follow-up time; or death from thyroid cancer. A mean TSH score was calculated for each patient by averaging all available TSH determinations, where 1 = undetectable TSH; 2 = subnormal TSH; 3 = normal TSH; and 4 = elevated TSH. Patients were also grouped by their TSH scores: group 1: mean TSH score 1.0-1.99; group 2: mean TSH score 2.0-2.99; group 3: mean TSH score 3.0-4.0. The degree of TSH suppression did not differ between papillary and follicular thyroid cancer patients. However, TSH suppression was greater in papillary cancer patients who were initially classified as being at higher risk for recurrence. This was not the case for follicular cancer patients, where TSH suppression was similar for all patients. For all stages of papillary cancer, a Cox proportional hazards model showed that disease stage, patient age, and radioiodine therapy all predicted disease progression, but TSH score category did not. However, TSH score category was an independent predictor of disease progression in high risk patients (p = 0.03), but was no longer significant when radioiodine therapy was included in the model (p = 0.09). There were too few patients with follicular cancer for multivariate analysis. These data suggest that physicians use greater degrees of TSH suppression in higher risk papillary cancer patients. Our data do not support the concept that greater degrees of TSH suppression are required to prevent disease progression in low-risk patients, but this possibility remains in high-risk patients. Additional studies with more patients and longer follow-up may provide the answer to this important question.

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.

[Medullotherapy in hematopoietic depression]. / O medulloterapii pri depressii krovetvoreniia.

Many-year observations, made by the authors, indicated that the main mechanism of medullotherapy is healing of histocompatible allogenic bone marrow, transplanted against the background of immunosuppressive therapy. In patients with hyperplastic anemia bone marrow transplantation results in a persistant clinico-hematologic remission. Observations, made by the workers of the Leningrad Institute of Hematology and Blood Transfusion, have demonstrated that transplantations of the preserved autologous bone marrow to patients with malignant neoplasms contribute to the restoration of hemopoiesis, suppressed by high doses of chemical drugs and associated radiotherapy.

[Clinical morphological, cytogenetic and genealogical studies of patients with chronic monocytic leukemia]. / Kliniko-morfologicheskie, tsitogeneticheskie i genealogicheskie issledovaniia u bol'nykh khronicheskim monotsitarnym leikozom.

The introduction in clinical practice of modern methods of cytogenetic assays offers new opportunities in studying the nature of leukemia. Up to date, however, no due attention was given to the recognition of chromosome disorders in patients with chronic monocytic leukemia (CML). Study on the karyotype in 20 patients with chronic monocytic leukemia indicated that chromosome anomalies lie in both the changed chromosome number and their structure, in the phase of marked clinical manifestations these changes being increased, while in the stage of remission--being reduced. A rather high incidence of malignancies in near relations of patients with CML supports a suggestion of the related pathogenetic mechanisms underlying leukemia and malignant tumors.

Approach to the patient with advanced differentiated thyroid cancer.

Patients with advanced thyroid cancer may benefit from l-thyroxine treatment at doses that suppress serum TSH level, local treatment interventions, and radioiodine therapy. In those patients who are refractory to radioiodine therapy and in whom progressive disease has been documented, the efficacy of cytotoxic chemotherapy is poor. Encouraging results have been obtained with the use of kinase inhibitors that should be offered as first-line treatment, preferably in the context of a prospective trial.