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Objective. To study histopathology of the thyroid and parathyroid glands in HIV-infected African Americans in the United States. Methods. A retrospective review of 102 autopsy cases done by the Department of Pathology at Howard University Hospital from 1980 through 2007 was conducted. The histopathological findings of the thyroid and parathyroid glands were reviewed, both macroscopically and microscopically. A control group of autopsy patients with chronic non-HIV diseases was examined. Results. There were 71 males (70%) and 31 females (30%) with an average age of 38 years (range: 20-71 y). Thirteen patients with abnormal thyroid findings were identified. Interstitial fibrosis was the most common histological finding (4.9%), followed by thyroid hyperplasia (1.9%). Infectious disease affecting the thyroid gland was limited to 2.9% and consisted of mycobacterium tuberculosis, Cryptococcus neoformans, and cytomegalovirus. Kaposi sarcoma of the thyroid gland was present in only one case (0.9%). Parathyroid hyperplasia was the most common histological change noted in the parathyroid glands. Comparing the histological findings of cases and controls, we found a similar involvement of the thyroid, with a greater prevalence of parathyroid hyperplasia in HIV patients. Conclusion. Thyroid and parathyroid abnormalities are uncommon findings in the HIV-infected African American population.

Objective: To address the likelihood of thyroid malignancy for each cytologic interpretation, highly cellular and benign vs. follicular carcinoma, with particular attention to the indeterminate cytologic result, follicular neoplasm., Study Design: We retrospectively reviewed thyroid nodule cytologic and histologic interpretations from 1994 to 2002 in a tertiary medical center setting. Patients were referred for evaluation of thyroid nodules found incidentally or on physical examination., Results: A total of 886 thyroid nodules were aspirated in 802 patients (500 benign, 195 indeterminate, 129 inadequate, 62 malignant). Of 195 indeterminate lesions, 180 were classified as follicular neoplasm or "cannot rule out/possible" follicular neoplasm, with 144 of these ultimately removed and with malignant histologic findings in 28. Any mention of follicular neoplasm in the cytology report conferred a 19.4% risk of malignancy in patients who went on to surgery (including an unexpected 18.2% rate of malignancy in the subcategory in which a possible follicular neoplasm was a secondary listing in an otherwise-benign cytologic differential diagnosis)., Conclusion: There was no difference in the likelihood of histologic malignancy between the cytologic subcategories of "definite "follicular neoplasm and "cannot rule out/possible" follicular neoplasm. We recommend that cytologic reports on fine needle aspiration of thyroid nodules with a diagnosis of follicular neoplasm reflect this fact.

Objective: To review the pathogenesis as well as the clinical and laboratory features of catecholamine-induced cardiomyopathy associated with pheochromocytoma and other disorders and discuss the various treatment options available., Methods: Materials used for this article were identified through MEDLINE, PubMed, and Google Scholar searches of the relevant literature from 1955 to the present., Results: Catecholamines and their oxidation products cause a direct toxic effect on the myocardium. Catecholamines also exert a receptor-mediated effect on the myocardium. Catecholamine-mediated myocardial stunning has been implicated in the pathogenesis of stress-induced cardiomyopathy. Biopsy of the myocardium in patients with pheochromocytoma or those with stress-induced cardiomyopathy shows similar pathologic findings. The clinical features in pheochromocytoma-related cardiomyopathy include hypertension, dilated or hypertrophic cardiomyopathy, pulmonary edema due to cardiogenic and noncardiogenic factors, cardiac arrhythmias, and even cardiac arrest. Stress-related cardiomyopathy such as takotsubo cardiomyopathy occurs primarily in postmenopausal women. These patients may present with clinical features suggestive of an acute myocardial infarction or a hemodynamically compromised state. The definitive management of cardiomyopathy associated with pheochromocytoma includes medical treatment with alpha-adrenergic blockade, possibly along with angiotensin converting enzyme blockers and beta1-adrenergic receptor blockers, followed by excision of the tumor. Stress-induced cardiomyopathy is usually self-limiting; patients may require support with nonadrenergic inotropes., Conclusion: Recognition of catecholamine-induced cardiomyopathy, especially in patients with pheochromocytoma, before surgical treatment is important to minimize morbidity and mortality.

Objective: Surgery-induced thyroiditis can pose a significant clinical problem that is underappreciated. We present a case of new-onset atrial fibrillation as a consequence of palpation thyroiditis in a 70-year-old man who underwent radical right neck dissection for malignant melanoma and review the limited literature on this topic., Design: Biochemical parameters including thyrotropin, free thyroxine, triiodothyronine, erythrocyte sedimentation rate, C-reactive protein, thyroglobulin, thyroid stimulating immunoglobulins, thyroid binding inhibitory immunoglobulins, thyroid peroxidase, thyroglobulin antibodies, and 24-hour urine iodine were measured. Thyroid ultrasound and technetium-99m pertechnetate scintigraphy with radioactive iodine 131 uptake were employed for diagnostic purposes., Main Outcome: Following right neck exploratory dissection, the patient developed hyperthyroidism and atrial fibrillation. Imaging studies were compatible with right lobar thyroiditis. Other etiologies of thyroiditis were excluded. Despite normalization of thyroid function after 2 weeks, atrial fibrillation persisted and required cardioversion., Conclusions: Manipulation of the thyroid gland during neck exploratory surgery can result in hyperthyroidism with atrial fibrillation as a consequence. To avoid this complication, careful attention should be paid during surgical procedures or other clinical situations in which the thyroid gland is manipulated.

Objective: To describe a patient with a histologically proven pancreatic glucagonoma, noted incidentally during a follow-up visit for high aminotransferase levels, and to evaluate its autonomy with a standard 75-g oral glucose tolerance test., Methods: We present the results of a 2-hour oral glucose tolerance test, with plasma glucagon and blood glucose levels measured every 30 minutes after an oral glucose load. In addition, we provide a brief review of the literature on the diagnosis and management of glucagonomas and the importance of long-term surveillance., Results: In our patient, who had a 1-year history of impaired fasting glucose, plasma glucagon levels were persistently suppressed to within the normal range after oral glucose challenge. Octreotide scintigraphy revealed abnormal uptake in the pancreatic tail, and a 2.8-cm mass was removed at laparoscopic distal pancreatectomy. Immunohistochemical staining of the tumor tissue showed intense reactivity for glucagon. Plasma glucagon levels were reduced to <50 pg/mL postoperatively, and scintigraphic study at 4-month follow-up showed no residual uptake at the previous tumor site or elsewhere., Conclusion: Glucagon-secreting pancreatic tumors are extremely rare. A substantially elevated plasma level of glucagon is usually seen in patients with metastatic tumors. In the early stage of a glucagonoma, however, the plasma glucagon level may be only modestly elevated and may still be susceptible to normal negative feedback inhibition. We demonstrated plasma glucagon complete suppressibility after oral glucose challenge in a patient with a glucagonoma, the first such report in the literature.

Papillary thyroid carcinoma (PTC) commonly metastasizes to cervical lymph nodes. Distant metastases are unusual with the lungs most frequently involved. Well-differentiated thyroid carcinoma very rarely presents with metastases to the spleen. This is the case of a 25-year-old man with a history of PTC (1.4 cm primary; no capsular invasion and negative lymph node metastases). One year after initial surgery, recurrent disease was found in multiple neck nodes by central neck dissection. Whole body scan (WBS) following a therapeutic ablation dose of 150 mCi I(131) revealed mediastinal metastases. Computerized axial tomography (CT) of the chest one year later showed no gross mediastinal or pulmonary disease. However, multiple large splenic lesions were incidentally noted. Evaluation by ultrasound (US) showed lesions to be solid echogenic masses without remarkable Doppler characteristics to suggest vascular tumors. US-guided percutaneous fine-needle aspiration biopsy (FNAB) of one lesion was nondiagnostic. After withdrawal from Levothyroxine, serum TSH was >100 mU/L with a thyroglobulin of 9.4 ng/mL and negative anti-thyroglobulin antibodies. Diagnostic WBS revealed faint splenic uptake but was otherwise unremarkable. Following treatment with 192 mCi I(131), WBS demonstrated increased activity in the mediastinum as well as in the spleen suggesting mediastinal and splenic metastases. Contrast CT of the abdomen showed multiple low-attenuated heterogeneously enhancing splenic masses, normal liver and no intra-abdominal lymphadenopathy. The largest mass (4.5 x 3.5 cm) was exophytic and in close proximity to the splenic capsule. Despite the serum thyroglobulin of only 9.4 ng/mL, the finding of I(131) accumulation within solid splenic masses led to a preoperative diagnosis of thyroid carcinoma metastases. To establish the diagnosis and to remove the risk for splenic rupture, a laparoscopic splenectomy was performed. Histopathologic analysis showed large littoral cell angiomas (LCA). False-positive radioiodine scintigraphy in the setting of PTC involving a vertebral hemangioma has been reported. To our knowledge, this is the first case that describes multiple angiomas mimicking metastatic thyroid carcinoma to the spleen. In one-third of all cases reported, LCA co-exists with various visceral organ cancers or malignant lymphoma. This is the first report of an association between LCA and thyroid carcinoma.

One hundred sixty-four (164) healthy, young Caucasian women enrolled as midshipmen at the United States Naval Academy with no known disease or bone injury were followed for 3.6 years. Change in bone mineral density (BMD) of the hip, lumbar spine and distal tibia, and total body bone mineral content (TBMC) was measured by dual energy X-ray absorptiometry (DXA). Bone mineral density and TBMC of these women were measured within 2 months (60 +/- 4 days) of entering the Academy and annually. Over the study period, hip BMD increased 2.26% (P < 0.001), lumbar spine BMD increased 3.27% (P < 0.001) and distal tibia BMD increased 5.2% (P < 0.001). Total body bone mineral content showed a 5.25% (P < 0.001) increase during the study period. In this group of young women, gain in BMD and TBMC continued until age 22. These results suggest that bone mass may accrue in certain groups of women beyond age 22. The significance of this increase in bone mass during early adulthood on risk for osteoporotic fractures in later life and its impact on exercise-related bone injuries are unknown and warrant further examination.

Context: Standard therapy for patients with primary hypothyroidism is replacement with synthetic thyroxine, which undergoes peripheral conversion to triiodothyronine, the active form of thyroid hormone. Within the lay population and in some medical communities, there is a perception that adding synthetic triiodothyronine, or liothyronine, to levothyroxine improves the symptoms of hypothyroidism despite insufficient evidence to support this practice., Objective: To evaluate the benefits of treating primary hypothyroidism with levothyroxine plus liothyronine combination therapy vs levothyroxine monotherapy., Design, Setting, and Patients: Randomized, double-blind, placebo-controlled trial conducted from May 2000 to February 2002 at a military treatment facility that serves active duty and retired military personnel and their family members. The trial included a total of 46 patients aged 24 to 65 years with at least a 6-month history of treatment with levothyroxine for primary hypothyroidism., Intervention: Patients received either their usual dose of levothyroxine (n = 23) or combination therapy (n = 23), in which their usual levothyroxine dose was reduced by 50 micro g/d and substituted with liothyronine, 7.5 micro g, taken twice daily for 4 months., Main Outcome Measures: Scores on a hypothyroid-specific health-related quality-of-life (HRQL) questionnaire, body weight, serum lipid levels, and 13 neuropsychological tests measured before and after treatment., Results: Serum thyrotropin levels remained similar and within the normal range in both treatment groups from baseline to 4 months. Body weight and serum lipid levels did not change. The HRQL questionnaire scores improved significantly in both the control group (23%; P<.001) and the combination therapy group (12%; P =.02), but these changes were statistically similar (P =.54). In 12 of 13 neuropsychological tests, outcomes between groups were not significantly different; the 1 remaining test (Grooved Peg Board) showed better performance in the control group., Conclusion: Compared with levothyroxine alone, treatment of primary hypothyroidism with combination levothyroxine plus liothyronine demonstrated no beneficial changes in body weight, serum lipid levels, hypothyroid symptoms as measured by a HRQL questionnaire, and standard measures of cognitive performance.

Objective: To compare the clinical and biochemical features, bone densitometry data, and results of diagnostic imaging to localize parathyroid tumors in patients with radiation-associated hyperparathyroidism (R-HPT) and patients with HPT who had no history of radiation exposure (NR-HPT)., Methods: We performed a retrospective analysis of 34 patients with HPT who underwent evaluation and subsequent neck exploration between 1990 and 1995. We recorded and compared the symptoms, biochemical findings, bone densitometry data, results of diagnostic imaging, and pathologic findings in R-HPT and NR-HPT groups., Results: The R-HPT group (8 men and 4 women)generally was older than the NR-HPT group (14 men and 8 women), but the age difference was not statistically significant. Patients in the R-HPT group had received radiotherapy (6.9 to 21.7 Gy) between 2 and 9 years of age for various diagnoses. Eight patients (67%) in the R-HPT group and 13 (59%) in the NR-HPT group had no symptoms of HPT. The rest of the patients in both groups had nonspecific symptoms, such as fatigue and dyspepsia. Four patients (18%) in the NR-HPT group had nephrolithiasis, and 3 (14%) had skeletal manifestations at initial assessment. Serum calcium, phosphorus, and parathyroid hormone levels and 24-hour urine calcium excretion were similar in both groups. Mean lumbar spine bone mineral density was lower in women in the R-HPT group than in those in the NR-HPT group, but the prevalence of osteoporosis did not differ significantly in the two study groups. Sestamibi scintigraphy accurately localized adenomas in both groups equally well (sensitivity >90%). In the R-HPT group, 11 patients had a single parathyroid adenoma and 1 had hyperplasia of all four parathyroid glands. In the NR-HPT group, 21 patients had a single parathyroid adenoma and 1 had parathyroid hyperplasia. In nine patients in the R-HPT group, ultrasonography showed thyroid nodules >1 cm. Pathologic examination of surgical specimens in the R-HPT group confirmed thyroid carcinoma in 11 patients ( 10 papillary and 1 follicular can-cer); no patient in the NR-HPT group had thyroid cancer. Six weeks after thyroidectomy, patients with thyroid can-cer received 1311 (mean dose, 145 mCi), five of whom needed additional 1311 treatments., Conclusion: Patients with a history of childhood neck irradiation who have HPT have a high likelihood of coexisting thyroid cancer. This observation may justify surgical exploration rather than vigilant follow-up in asymptomatic patients with primary HPT and coexisting thyroid nodules who have a history of radiation exposure.

Objective: To improve glycemic control by substituting saturated fat for starch, to identify any adverse effect on lipids masked by the extensive use of metformin and lipid-lowering drugs, and to attempt to separate dietary effects from effects of multiple drugs., Methods: We undertook a retrospective review of medical records of patients who completed 1 year of follow-up after dietary prescription. The study subjects included 151 patients in the diet group (whose dietary instructions included high saturated fat but starch avoidance) and 132 historical control subjects (who were allowed unlimited monounsaturated fat but had restriction of starch in their diets)., Results: Hemoglobin A1c (HbA1c) levels improved in both study groups (-1.4 +/- 0.2% [P<0.001]; 95% confidence interval [CI], -1.9 to -0.9). Use of metformin was associated with a decrease in HbA1c (-0.12 +/- 0.003%/mo [P<0.001]; 95% CI, -0.17 to -0.07). The diet group had an additional decrease of -0.7 +/- 0.2% (P<0.001; 95% CI, -1.1 to -0.3). Weight increase was associated with the use of insulin (+0.3 +/- 0.07 kg/mo [P<0.001]; 95% CI, 0.2 to 0.5), sulfonylurea (+0.18 +/- 0.06 kg/mo [P<0.01]; 95% CI, 0.05 to 0.30), and troglitazone (+0.7 +/- 0.2 kg/mo [P<0.005]; 95% CI, 0.3 to 1.2). Although not statistically significant, metformin therapy showed a trend for weight loss (-0.14 +/- 0.08 kg/mo; P = 0.07). An additional weight loss was noted in the diet group (-2.65 +/- 0.62 kg [P<0.001]; 95% CI, -3.87 to -1.44). Hydroxymethylglutaryl-coenzyme A reductase inhibitor use was associated with reduced total cholesterol level (-1.7 +/- 0.6 mg/dL per month [P<0.005]; 95% CI, -2.9 to -0.5). The diet group had an additional decrease of -13.0 +/- 4.5 mg/dL (P<0.001; 95% CI, -21.9 to -4.1). No significant effect of the diet on triglyceride, low-density lipoprotein, or high-density lipoprotein levels was detected., Conclusion: Addition of saturated fat and removal of starch from a high-monounsaturated fat and starch-restricted diet improved glycemic control and were associated with weight loss without detectable adverse effects on serum lipids.

Eighty-six healthy, young Caucasian 18-year-old men with no known disease or bone injury were recruited to this study at the United States Naval Academy. Change in bone mineral density (BMD) of the hip, lumbar spine, and distal tibia, and total body bone mineral content (TBMC) was measured by dual-energy X-ray absorptiometry (DXA). BMD and TBMC of these men were measured within 2 months (67 +/- 3 days) of entering the Academy, and, at the end of their first, second, and fourth years. Hip BMD was unchanged during the study period (p > 0.05). Lumbar spine BMD increased 3% (p < 0.001) and distal tibia BMD increased 5% (p < 0.001). TBMC showed a 7.5% increase over the study period. In this group of young men, gain in BMD and TBMC is greatest to age 21 years, with minimal further increase after age 21. The significance of this rise in bone mass during early adulthood on risk for osteoporotic fractures in later life or its impact on exercise-related bone injuries is unknown and warrants further examination.

Usual causes of intolerance to thyroxine sodium include coronary artery disease, advanced age, untreated adrenal insufficiency, and severe hypothyroidism. We describe 4 patients with iron deficiency anemia and primary hypothyroidism. After treatment with thyroxine sodium, these patients developed palpitations and feelings of restlessness, which necessitated discontinuation of the thyroid hormone. After the anemia was treated with ferrous sulfate for 4 to 7 weeks, they were able to tolerate thyroxine sodium therapy. Iron deficiency anemia coexisting with primary hypothyroidism results in a hyperadrenergic state. In such patients, we postulate that thyroid hormone administration causes palpitations, nervousness, and feelings of restlessness. Correction of any existing pronounced anemia in hypothyroid patients who are intolerant to thyroxine sodium therapy may result in tolerance to this agent.

Objective: To assess the efficacy of alendronate therapy on bone mineral density (BMD) at the lumbar spine and hip in men with osteoporosis., Methods: Medical records of male patients with osteoporosis, who had undergone follow-up in the Endocrinology Clinic at the National Naval Medical Center, were reviewed, and nine patients treated with alendronate for at least 1 year were identified. Patients were excluded from analysis if they had evidence of osteomalacia or if baseline and follow-up BMD results on the same dual-energy x-ray absorptiometry (DEXA) densitometer, at least 10 months apart, were not available. DEXA BMD results at the lumbar spine and hip, before and after at least 10 months of alendronate treatment, were analyzed for significant differences. Patients were also receiving calcium supplementation (1,000 to 1,500 mg/day), and all but one patient received vitamin D (400 to 800 U/day)., Results: Lumbar spine BMD increased by 6.4 +/- 1.8% per year with alendronate treatment (P = 0.008). A mean absolute gain of 0.052 +/- 0.010 g/cm 2 (P = 0.005) in lumbar spine BMD was noted for the entire study group (N = 9), after a mean duration of treatment of 14 +/- 1 months. The mean lumbar spine BMD Z score improved by 0.40 +/- 0.09 (P = 0.002) with alendronate therapy. The femoral neck BMD also increased by 4.5 +/- 1.4% per year with alendronate treatment (P = 0.013). The mean absolute gain in femoral neck BMD was 0.028 +/- 0.009 g/cm 2 (P = 0.013) for the study group (N = 9) after 14 +/- 1 months of therapy. The mean femoral neck BMD Z score improved 0.30 +/- 0.08 (P = 0.005) with treatment. BMD gains at the greater trochanter of 3.2 +/- 1.5% per year (P = 0.067) and at Ward's triangle of 9.1 +/- 4.2% per year (P = 0.061) were not statistically significant. Two patients discontinued alendronate treatment after 1 year because of epigastric or retrosternal pain., Conclusion: Oral alendronate treatment, given in combination with calcium supplementation and physiologic doses of vitamin D, resulted in significant improvements in lumbar spine and femoral neck BMD after a 14-month period in this small group of men with osteoporosis. Although controlled, prospective trials involving larger numbers of male patients with fracture incidence data are needed before definitive conclusions can be made, alendronate treatment seems to be effective in improving BMD in men with osteoporosis, similar to its efficacy in women.

Purpose: To examine the effects of propylthiouracil (PTU) pretreatment on the outcome of initial I-131 therapy for Graves' disease., Design: A retrospective chart review was done., Patients and Methods: The authors studied 106 patients in an outpatient nuclear medicine setting who were given initial I-131 therapy for Graves' disease from September 1989 to March 1993 and followed for at least 6 months after therapy. These patients were divided into groups based on whether they had ever received PTU or, if they had received PTU, the length of time between the last dose of PTU and the I-131 therapy dose. Measured failure rates of initial I-131 therapy were based on recurrent or continued hyperthyroidism., Results: Treatment failure rates increased markedly from 2.5% in non-PTU-treated patients (n = 80) to 23.1% (n = 26) in patients pretreated with PTU (P = 0.003). Although not significant, two PTU-pretreated subgroups showed a trend toward increased failure rates. The failure rate was 15.4% (n = 13) in patients whose last dose of PTU was 7-14 days before I-131 therapy, and it increased further to 30.8% (n = 13) in patients whose last dose of PTU was within 1 week of I-131 therapy., Conclusions: PTU pretreatment within 2 weeks of I-131 treatment is a strong independent risk factor in failure rates after initial I-131 therapy in patients with Graves' disease. Patients should be free of PTU for 2 weeks before I-131 therapy if they are able to tolerate it, otherwise the dose of I-131 may need to be adjusted upward to diminish the risk that the initial I-131 therapy will fail.

Parathyroid carcinoma is a rare endocrine malignancy characterized by the exaggerated metabolic effects of the parathyroid glands. The preoperative differential diagnosis between parathyroid carcinoma and primary hyperparathyroidism is often difficult because many of the signs and symptoms are very similar. Intraoperative differentiation is obscured by the strict anatomic and histologic criteria required for diagnosis of parathyroid carcinoma. We have encountered three patients with parathyroid carcinoma during the last 10 years and managed them successfully. Two of them presented with recurrence of hypercalcemia, one 11 years after and the other 3 years after the primary operation for hyperparathyroidism; both patients were eventually diagnosed with parathyroid carcinoma. The third case was suspected as primary hyperparathyroidism preoperatively but confirmed as carcinoma subsequent to histologic examination.

Objective: To assess the clinical utility of bone mineral density (BMD) of Ward's triangle by dual-energy absorptiometry (DEXA) as an indicator of osteoporosis in comparison with quantitative computed tomography (QCT) of the lumbar spine and DEXA of the lumbar spine and hip sites (trochanter and femoral neck)., Methods: We conducted a retrospective study of all patients (28 men and 17 women) with decreased BMD by QCT (T-score less than -1.0) who had DEXA BMD performed at the lumbar spine and hip between October 1993 and January 1995 in our Endocrine Clinic., Results: Osteoporosis based on the World Health Organization criteria (T-score less than -2.5) was defined by QCT lumbar spine BMD in 78% of the study subjects and by DEXA of Ward's triangle in 53%, of the femoral neck in 22%, of the trochanter in 7%, and of the lumbar spine in 2%. In the men, the only DEXA BMD measurement that was sensitive for detecting osteoporosis was Ward's triangle. Of the 24 men with osteoporosis by QCT BMD, 14 were defined as having osteoporosis by DEXA exclusively at Ward's triangle. The DEXA lumbar spine BMD measurement was actually above the mean for young normal control subjects in 8 of the 24 men with osteoporosis by QCT BMD. In the 11 women with osteoporosis by QCT BMD, the DEXA BMD at Ward's triangle and the femoral neck were equally sensitive in detecting osteoporosis, whereas the DEXA lumbar spine and trochanter BMD measurements were insensitive., Conclusion: DEXA BMD of Ward's triangle is a sensitive indicator of osteoporosis, particularly in men, and should be used to identify patients at increased risk for osteoporosis-related fractures.

Recent studies have shown that under experimental conditions ferrous sulfate may reduce the gastrointestinal absorption of orally administered levothyroxine sodium in patients with primary hypothyroidism. We describe a patient who became hypothyroid while taking ferrous sulfate. The hypothyroid status was corrected by increasing the dose of levothyroxine. Subsequently, when ferrous sulfate was discontinued, the patient became hyperthyroid while taking the higher dose of thyroid hormone preparation. Since both hypothyroidism and iron deficiency anemia may coexist, additional thyroid function testing is recommended in patients treated concurrently with ferrous sulfate and L-thyroxine.

Objective: To alert clinicians to the potential interaction between warfarin and hyperthyroidism., Methods: We present two case reports and compare findings with those in a control population of patients with hyperthyroidism who were not receiving anticoagulant therapy., Results: In two patients, severe coagulopathy was precipitated by the interaction of warfarin and increased thyroid hormone levels. In both cases, the patients also demonstrated resistance to vitamin K therapy, which persisted for several days. We also studied five control patients with hyperthyroidism who were not taking anticoagulant drugs; no effect of thyroid hormone on the plasma levels of vitamin K-dependent clotting factors was noted. One of our patients with hyperthyroidism who was taking warfarin had levels of warfarin in the serum that were 5 times the therapeutic range; this finding suggests that the protein binding or absorption of warfarin may be altered in such patients., Conclusion: Multiple factors may contribute to the enhanced effect of warfarin seen in patients with hyperthyroidism, including altered metabolism of vitamin K-dependent clotting factors, altered metabolism of warfarin, or decreased protein binding of the drug. Patients with hyperthyroidism should be given lower doses of warfarin to avoid severe coagulopathy.

Objective: To characterize a disorder of episodes of flushing and increased levels of 5-hydroxyindoleacetic acid (5-HIAA) in men with secondary hypogonadism who respond to testosterone therapy., Material and Methods: We present detailed case reports of three male patients who had flushing, secondary hypogonadism, and increased urinary 5-HIAA levels and describe their clinical and laboratory features before and after treatment with testosterone. In addition, six male patients with hypogonadism (three with primary and three with secondary hypogonadism) without flushing were assessed., Results: The three patients with flushing and secondary hypogonadism (serum total testosterone 5.45 +/- 0.63 nmol/L, free testosterone 89.3 +/- 7.0 pmol/L, follicle-stimulating hormone 3.85 +/- 0.58 IU/L, and luteinizing hormone 4.41 +/- 0.98 IU/L) had increased urinary 5-HIAA levels (98.5 +/- 12.2 micromol/24 h) but normal blood serotonin levels (9.66 +/- 1.58 micromol/L). During a pentagastrin-calcium stimulation test, serum calcitonin and blood serotonin values were normal in patients with secondary hypogonadism and flushing. Detailed investigation showed no evidence of a carcinoid tumor. Urinary 5-HIAA levels became normal (16.6 +/- 1.73 micromol/24 h) after treatment with testosterone. When testosterone therapy was discontinued in two patients, flushing and increased urinary 5-HIAA levels recurred. Furthermore, flushing and the elevated urinary 5-HIAA values resolved when testosterone treatment was reinitiated. The six patients with hypogonadism without flushing had normal urinary 5-HIAA levels (14.9 +/- 3.31 micromol/24 h)., Conclusion: Male patients with flushing and increased urinary 5-HIAA levels should undergo assessment for hypogonadism after screening for carcinoid tumor. If hypogonadism is diagnosed, resolution of flushing and normalization of 5-HIAA may be achieved with testosterone treatment. We suggest that pseudocarcinoid syndrome associated with hypogonadism be the descriptive label used for this combination of clinical features.

A case of galactorrhea caused by painful esophagitis, a previously unreported etiology, is presented. The galactorrhea promptly resolved with appropriate treatment of the esophagitis. It is proposed that the mechanism of production of galactorrhea is similar to that seen with chest wall lesions. This cause should be kept in mind when evaluating unusual causes of galactorrhea.

Objective: To evaluate the effects of nicotinic acid on serum thyroid hormone levels in the absence of systemic illness or hepatic dysfunction., Design: We determined the effect of treatment with nicotinic acid on serum thyroid hormone levels in one female and four male patients (mean age, 44.4 years) with hyperlipidemia., Material and Methods: In the five study patients, we measured serum lipids in conjunction with serum thyroxine (T4), triiodothyronine (T3) resin uptake, T3, free T4, thyroid-stimulating hormone (TSH), and thyroxine-binding globulin before, during, and after treatment with nicotinic acid., Results: Serum lipid levels responded appropriately to nicotinic acid treatment. Thyroid function studies done a mean of 1.3 years (range, 0.5 to 3.5) after initiation of nicotinic acid therapy (mean daily dose, 2.6 +/- 0.7 g) revealed significant decreases in serum levels of total T4 (21%), free T4 index (16%), T3 (13%), and thyroxine-binding globulin (23%) (P < 0.02), whereas no significant changes were noted in free T4, T3 resin uptake, and TSH levels. During the course of treatment, the patients, who were carefully questioned, had no symptoms of hypothyroidism. Hypothyroidism was further excluded in three patients who had a normal serum TSH response to administration of thyrotropin-releasing hormone. In two patients, measurements of thyroid function returned to pretreatment levels after discontinuation of nicotinic acid therapy. No patient had significant abnormalities in liver-associated enzymes or evidence of systemic illness during the course of treatment., Conclusion: These results suggest that nicotinic acid decreases serum thyroid hormone concentrations while maintaining a euthyroid state. This effect may be mediated through reduction in thyroxine-binding globulin, but other mechanisms may also be involved.

Non-thyroidal illness is classically associated with a low total triiodothyronine (T3) level. Episodes of severe recurrent dental pain unassociated with fever or systemic infection in a patient was marked 2 to 3 weeks later by low T3 levels (56 ng/ml). Other thyroid and metabolic tests were normal. T3 levels returned to normal on resolution of pain. Recurrence of a transient, mild episode of pain was not associated with a low T3 2 weeks after its onset. We suggest that T3 levels may be markers for severe pain and suffering or disturbances responsible for pain and suffering in patients receiving analgesics.

Although the action of gastric inhibitory polypeptide (GIP) on the beta cells of the pancreas is well documented, the effect of this hormone on insulin secretion in patients who are hypothyroid has not been studied. Hypothyroid patients demonstrate increased serum immunoreactive insulin levels in response to oral glucose when compared with euthyroid subjects. We postulated that a delayed and exaggerated response of GIP could account for the hyperinsulinaemic response. Nine thyroidectomized patients (aged 44.9 +/- 3.6 years) who were otherwise healthy but undergoing re-evaluation for recurrence of thyroid carcinoma, were given a 75 g oral glucose tolerance test (OGTT). These subjects were studied 6 weeks after thyroid hormone replacement had been stopped and while on hormone treatment. The serum glucose and plasma GIP responses to oral glucose were similar in the euthyroid and hypothyroid states. The serum insulin response as well as the areas under the curve for insulin following OGTT were significantly elevated (P < 0.01) during hypothyroidism. Solid-phase gastric emptying times studied in six patients who were euthyroid and hypothyroid were not different (35 +/- 12 versus 36 +/- 14 min respectively). None of the subjects had detectable levels of serum thyroglobulin, microsomal or parietal cell antibodies. In summary, we have confirmed a hyperinsulinaemic response to an OGTT and normal solid-phase gastric emptying rates in this form of hypothyroidism. We did not find significant differences in serum glucose or GIP responses and postulate this as evidence of resistance to the effects of endogenous insulin. The mechanism of alterations in carbohydrate tolerance in the hypothyroid state continue to remain unknown.

Cowden's Disease or multiple hamartoma syndrome is an autosomal dominant genodermatosis associated with abnormalities of the breast, thyroid gland, gastrointestinal tract and genitourinary system. A large percentage of these patients have goiters or other thyroid abnormalities. Physicians should consider the diagnosis of Cowden's disease in patients presenting with thyroid disease and skin lesions such as papules or skin tags and if present these subjects should be screened for other malignancies associated with this disease.

Generalized resistance to thyroid hormone is a rare condition; affected individuals have elevated serum levels of free thyroxine and free triiodothyronine with inappropriately normal or slightly elevated levels of thyrotropin, yet are generally clinically euthyroid. However, responsiveness to thyroid hormone varies from tissue to tissue, and some patients may benefit from treatment with exogenous hormone. We have described the case of a patient with this disorder who initially had a mildly elevated serum thyrotropin level and was clinically euthyroid but in whom symptomatic autoimmune hypothyroidism subsequently developed. The serum free thyroxine level, although diminished from its previously elevated value, remained within the normal range. The patient required substantial doses of levothyroxine to return basal and stimulated TSH to their prior levels. Criteria for the treatment of adults with this disorder have not been firmly established. This case suggests that one indication for thyroid hormone supplementation may be the presence of high-titer serum antithyroid antibodies in patients who initially have mildly elevated thyrotropin values; they could be at increased risk for progression to overt hypothyroidism.

The etiology of incidentally discovered, nonfunctional adrenal nodules was evaluated by using the 17-hydroxyprogesterone (17-OHP) response to synthetic adrenocorticotrophin (cosyntropin) (ACTH) administration. Patients who were discovered to have adrenal nodules and age-matched volunteers were studied. A total of 12 patients with adrenal nodules and 10 control subjects were studied. None of the patients with adrenal nodules had any evidence of hormonal hypersecretion consistent with pheochromocytoma, Cushing's syndrome or hyperaldosteronism. All subjects had serum 17-OHP and cortisol responses measured at baseline and at 30 and 60 min following the intravenous administration of 250 micrograms of ACTH. Baseline 17-OHP levels in patients with adrenal nodules were not significantly different from those of the normal controls (adrenal nodules 17-OHP: 75 +/- 13 vs control 68 +/- 11 ng/dl). After stimulation with ACTH, both 30 min and 60 min 17-OHP levels in patients with adrenal nodules (322 +/- 47 and 361 +/- 54 ng/dl, respectively) were significantly elevated over the responses seen with the controls (169 +/- 29 ng/dl at 30 min, p < 0.015, and 158 +/- 20 ng/dl at 60 min, p < 0.004). Baseline and post-ACTH serum cortisol levels were similar in both groups. Out of these twelve patients with adrenal nodules, nine were reevaluated twelve months later. In this group the basal 17-OHP remained comparable to normal levels (72 +/- 8.4 ng/dl) whereas the post-ACTH levels still remained exaggerated (30 and 60 min values 327 +/- 37 and 373 +/- 39 ng/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

A patient with Zollinger-Ellison syndrome (ZES) was found to have a solitary, extrapancreatic, extraintestinal gastrinoma in a peripancreatic lymph node. Preoperative studies did not show the location of the tumor. After excision of the gastrinoma the patient's fasting serum gastrin level dropped from preoperative levels of 596 pg/ml to 120 pg/ml (normal, less than 200 pg/ml). Fasting and stimulated gastrin levels have remained within the normal range at 18 months follow-up. This patient had previously undergone antrectomy, so it could not be determined if this tumor represented a primary lymph node gastrinoma or metastasis from an unrecognized tumor that may have been present in the resected stomach or duodenum. The outcome of this case confirms the previous reports that ZES can be controlled after resection of gastrinomas that were contained within abdominal lymph nodes, even if a primary enteropancreatic tumor is not found. Our results also support the use of an aggressive operative search aimed at eradication of the tumor in patients with ZES even if preoperative localization studies fail to identify the site of the gastrinoma.