Objective: To identify predictive factors of clinical outcome of subacute thyroiditis. Design: Retrospective case series of 56 consecutive patients treated in 3 outpatient clinics between 1999 and 2005. Medical records were reviewed for demographic data, seasonal disease distribution, laboratory and clinical course, treatment, and short-term outcome. Main outcome: Mean age was 48.6±12 yr; 70% were females. Twenty-five percent had antithyroid antibodies and 9% had recurrent disease. Differences in occurrence by season were not significant (p=0.28). Ultrasound, performed in 35 patients, revealed thyroid nodules in 25 (median size, 17 mm). Ten patients received no treatment, and 43 received either non-steroidal anti-inflamatory drugs (NSAID) (no.=25) or glucocorticoids (no.=18); data for 3 patients were missing. Median disease duration was 77 days; mean peak free T4 (FT4) level was 43.7±25.3 pmol/l. A hypothyroid phase was documented in 31 patients, and remained permanent in 6. Peak FT4 level, but not erythrocyte sedimentation rate or clinical score, was positively correlated with the highest TSH level and with disease duration. Untreated patients had less severe clinical disease than treated patients, but a similar outcome. Patients given glucocorticoids had a shorter overall disease duration (p=0.03), with no differences in duration of hyperthyroidism, peak FT4 or highest TSH levels, compared with patients given NSAID. Conclusion: Subacute thyroiditis follows an unpredictable clinical course that is hardly affected by its clinical features or treatment.

OBJECTIVE:We aimed to assess low-dose recombinant human thyroid-stimulating hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular goiters (MNGs) in elderly patients with comorbidities.DESIGN:This was a short-term, observational study.METHODS:We measured 24-h thyroid radioiodine uptake (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy. Thyroid volume was assessed by computed tomography at baseline and day 180.RESULTS:rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from 25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P < 0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH < 0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml; P < 0.01). Symptomatic relief, improved well-being, and/or reduction or elimination of antihyperthyroid medication were seen in 76% of patients. Three (18%) patients had transient neck pain or tenderness, or palpitations; one had transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by 3 months.CONCLUSIONS:Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30 mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly patients with comorbidities.

Hyponatremia associated with high urine osmolality is usually caused by inappropriate secretion of antidiuretic hormone. However, secondary hypoadrenalism is also accompanied by hyponatremia and with features indistinguishable from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). As secondary hypoadrenalism requires a specific treatment, a high index of suspicion and appropriate hormonal testing are required to differentiate between these two entities. We retrospectively studied 10 patients with a previously undiagnosed hypothalamic-pituitary disease who presented with an acute symptomatic hyponatremia. Mean age (±SD) was 65.1±8.4 yr. Mean serum sodium was 120.7±2.9 nmol/l and urinary osmolality, 453.9±74 mosmol/kg. Serum creatinine, urea and uric acid were low. Mean serum morning cortisol was low, 104.0±55.2 nmol/l. High-dose ACTH test showed adequate increment of serum cortisol in 3 out of 7 patients tested. Two of these 3 patients did not respond adequately to the low-dose ACTH test. Endocrine evaluation disclosed partial or complete hypopituitarism in all 10 patients. Six patients had pituitary macroadenomas, one had a craniopharyngioma, one patient had a large aneurysm of the internal carotid with sellar destruction and two others had empty sella. Treatment by fluid restriction did not affect serum sodium levels significantly. In contrast, all patients achieved normal sodium when treated by glucocorticosteroid. Central hypoadrenalism should be considered in any patient presenting with hyponatremia with high urine osmolality. Low-dose ACTH test should be performed and followed by appropriate endocrine and imaging studies. Hyponatremia in these patients is promptly corrected by glucocorticosteroid replacement.

BACKGROUND:Pituitary apoplexy is a rare major clinical event with neurological, neuro-ophthalmological, cardiovascular and hormonal consequences, resulting from an acute infarction of pituitary adenoma. We report our experience with a series of 40 patients presenting with pituitary apoplexy.PATIENTS:Forty patients (27 males, 13 females; mean age, 51.2 yr) were admitted to our medical center between years 1985-2002 with acute presentation of pituitary apoplexy. Visual field defects occurred in 61% and ocular paresis in 40% of subjects. Sixty-three percent of adenomas were nonfunctional, and prolactinomas comprised 31%.RESULTS:Thirty-four patients underwent transsphenoidal pituitary decompression. Visual fields and ophthalmoplegia improved in 81% and 71%, respectively. During follow-up (4.5+/-5.4 yr), 79% of patients developed hypogonadotrophic hypogonadism, central hypothyroidism appeared in 54% and hypocortisolism--in 40% of patients. Permanent diabetes insipidus was diagnosed in 8%. Serial sellar MRI showed disappearance of pituitary tumor in 63% of operated subjects. Six patients (3 with PRL-secreting and 3 nonfunctional adenomas) were treated medically (corticosteroids, dopamine agonists), two patients (out of three) with visual deficits improved, and tumor shrinkage was noted in four.CONCLUSIONS:We present a large series of patients with pituitary apoplexy. Most subjects were operated, but six were treated conservatively. Almost all patients improved clinically, including those who were not operated, but hormonal deficiencies are very common.

Many patients with cardiac arrhythmias require concomitant therapy with warfarin and amiodarone. Beyond the predictable pharmacokinetic drug-drug interaction requiring a significant warfarin dose reduction, the iodine-rich amiodarone affects the thyroid gland, causing overt hypothyroidism or thyrotoxicosis in 14%-18% of cases. In turn, thyroid disorders may affect warfarin sensitivity, with hypothyroidism and thyrotoxicosis resulting in increased or decreased warfarin requirements, respectively. We describe 3 patients on concomitant amiodarone and warfarin who developed amiodarone-induced thyrotoxicosis heralded by a significant decrease in warfarin requirements. We review the literature on the mechanisms of the complex drug-drug and drug-disease interactions within the thyroid gland, warfarin, and amiodarone triad. Given that significant thyroid disorders may be only mildly symptomatic and thus may escape clinical detection, we suggest that thyroid function should be tested in any patient with otherwise unexplained changes in warfarin dose requirements, particularly if concomitantly treated with amiodarone.

BACKGROUND:Treatment of patients with excessive anticoagulation is routinely done by intravenous phytonadione (vitamin K1). Oral administration of phytonadione has been shown to be an effective alternative to the intravenous route, but these methods have never been compared directly. Our objective was to compare efficacy and safety of intravenous vs oral phytonadione treatment in patients with excessive anticoagulation without bleeding. METHODS:The study was a prospective randomized controlled trial of consecutive patients presenting with excessive anticoagulation without major bleeding. Patients with a baseline international normalized ratio (INR) of 6 to 10 (n = 44, 47 episodes) received either intravenous or oral phytonadione (0.5 mg or 2.5 mg, respectively), and patients with an INR greater than 10 (n = 17, 19 episodes) received 1 mg or 5 mg, respectively. Efficacy and safety end points were sequential INR changes and the proportion of patients achieving therapeutic range (INR, 2-4), overcorrection (INR<2.0), or undercorrection (INR>4.0) INR values. RESULTS:Sixty-six episodes of excessive anticoagulation were studied. In patients with baseline INR 6-10 the response to intravenous phytonadione was more rapid than in the oral group, and the proportion of patients reaching therapeutic range INR at 6 hours (11/24 vs 0/23) and at 12 hours (16/24 vs 8/23) was significantly higher. However, mean +/- SD INR values were similar for both groups at 24 hours (2.9 +/- 0.8 vs 2.6 +/- 0.8). Patients in the intravenous group tended to be more often (7/24 vs 2/23) overcorrected (INR<2). In patients with baseline INR values greater than 10 efficacy and safety were comparable for both routes of administration. CONCLUSION:Oral administration of phytonadione had similar efficacy and safety as intravenously administered phytonadione and may be suitable for treatment of patients with excessive anticoagulation.

SummaryAdministration of vitamin K is the common mode of treatment in excessively anticoagulated patients. However, patient’s response to vitamin K varies, depending on the vitamin K dose and the route of administration. Another potential source of variation is the pre-treatment INR which has not been accounted for in most previous studies. In the present study the effect of baseline INR on the response to a single dose of intravenous vitamin K (0.5 mg) was studied in 95 episodes of excessively anticoagulated patients (n = 76).In 67 episodes of moderately excessive baseline INR (6-10) mean INR declined from 8.0 ± 1.2 to 2.6 ± 0.9 at 24 hours, 59/67 (88%) responding within the first 12 hours and not requiring a second dose. In contrast, in 28 episodes with highly excessive baseline INR (> 10) response was slower; mean INR declining from 13.6 ± 2.7 to 4.0 ± 2.1 at 24 hours. In 14/28 of these episodes, patients failed to respond to vitamin K in the first 12 hours and required a second vitamin K dose.We conclude that INR at presentation affects the response to vitamin K and that this INR value should be considered in determining appropriate vitamin K doses.

BACKGROUND:Primary hyperparathyroidism in elderly patients is usually associated with additional co-morbidity that increases operative risk, and thus many geriatric patients are denied the benefit of surgery for a single parathyroid adenoma.OBJECTIVES:To evaluate the safety and efficacy of accurate single photon emission computed tomography sestamibi scintigraphy, enabling precise localization of a single adenoma, in the geriatric population.METHODS:Twenty-two patients aged 70 years and over with biochemically proven PHPT and with a single parathyroid adenoma identified by localization studies (sestamibi SPECT scan and ultrasonography) underwent 23 operations over 29 months (out of a total of 140 patients operated upon during the same period). Immediate preoperative sestamibi scintigraphy and marking of focal adenoma uptake followed by intraoperative hand-held gamma probe were used for the removal of the parathyroid adenoma by unilateral minimal access surgery. Associated major co-morbid conditions and pre- and postoperative calcium, phosphorus and parathormone levels were recorded. Indications for surgery were listed and operative and postoperative complications were noted. The patients were followed for a mean period of 17.7 months using the same parameters.RESULTS:The 22 patients with PHPT had a mean age of 76.3 +/- 5.9 years (range 70-88 years) and a female to male ratio of 13:9. Associated co-morbidity included ischemic heart disease (n = 15), hypertension (n = 22), non-insulin-dependent diabetes mellitus (n = 9), chronic obstructive pulmonary disease (n = 3), and previous neck surgery (n = 3). Mean preoperative serum calcium, phosphorous and PTH were 11.7 +/- 1.3 mg/dl, 2.5 +/- 0.5 mg/dl and 160.9 +/- 75.4 pg/ml respectively. In 20 of the 22 patients, surgery was successful in curing PHPT (91%). One patient had persistent hypercalcemia due to a missed adenoma, and repeat operation (by focused minimal accesss surgery) was successfully performed 2 weeks later. There were no complications and no morbidity postoperatively. Mean postoperative serum calcium, phosphorous and PTH were 9.6 +/- 1.2 mg/dl, 3.0 +/- 0.5 mg/dl and 35.2 +/- 24 pg/ml respectively. In all patients, serum calcium levels remained normal (9.7 +/- 1.3 mg/ml) after long-term follow-up (mean 17.7 +/- 9.6 months).CONCLUSIONS:Minimally invasive, radio-guided focused parathyroidectomy for a single adenoma is a safe and effective method to cure hyperparathyroidism in the elderly. Success of surgery is directly related to the surgeon's experience and to the precise localization marking provided by sestamibi scintigraphic SPECT localization and concurrent sonographic findings.

Tumors of the thyroid and parathyroid glands may develop together or separately in patients who previously have been exposed to head and neck irradiation. Whether cranial irradiation confers an increased risk for pituitary adenoma remains unknown. We report the case of a 52-year-old woman who was treated during childhood for tinea capitis with scalp irradiation and later in life developed a prolactin-secreting tumor, a parathyroid adenoma, a benign thyroid lesion, and a basal cell carcinoma of the skin. She was treated successfully with bromocriptine and surgical removal of the parathyroid adenoma. Molecular analysis of the parathyroid tissue failed to demonstrate any abnormality of the multiple endocrine neoplasia Type 1 gene. This case report is the first to describe a prolactin-secreting tumor that developed in association with other endocrine neoplasia after head and neck irradiation. Our case suggests that multiple endocrine neoplasia may develop in a sporadic pattern after scalp irradiation.

OBJECTIVE:To compare patterns of osteoporosis health-related behaviors in peri and postmenopausal ultra-orthodox and secular Jewish women.METHODS:Interviews were conducted with 277 Israeli-Jewish women aged 45+. Health behaviors examined included: physical activity, smoking behavior, alcohol consumption, hormone replacement usage, screening behavior, calcium intake, pharmacological prevention, and help-seeking patterns. Correlates included demographic variables, health characteristics, knowledge, susceptibility beliefs, and familiarity with the disease.RESULTS:Low proportions of women in both groups participated in physical activities, but differed in type. Calcium intake was deficient in both groups. Education was the only correlate of calcium intake among secular women, and previous experience with the disease was the main determinant among orthodox women. Compared with the secular group, a considerably lower proportion of orthodox women reported using HRT or having performed a bone density examination. Orthodox participants' level of knowledge about osteoporosis was significantly lower as well. Education was an important correlate of knowledge in both groups, as was having performed a bone density examination. Higher age and being menopausal were important correlates of knowledge only for secular women. Having a family member suffering from the disease was associated with higher levels of knowledge among orthodox women. Marked differences were found in the participants' sources of information across groups.CONCLUSIONS:Findings emphasize the need to expand education in all areas of osteoporosis health-related behaviors among ultra-orthodox women, and in calcium intake and exercise for secular women as well. The transmission of the information should be adapted to the practices of each group.

We report a case of massive pulmonary embolus demonstrated on CT in a young woman presenting with dyspnea, with no known risk factors for embolism. Abdominal CT on further investigation showed a renal tumor invading the left renal vein and the inferior vena cava as the cause of the pulmonary embolus. In a patient presenting with pulmonary artery embolism without venous thrombosis, the differential diagnosis should include an occult tumor as the cause of the embolus.

We have retrospectively studied 41 patients with hypothalamic-pituitary disease and central hypothyroidism associated with hypopituitarism. Sixteen patients had nonsecreting pituitary macroadenoma, whereas different sellar and suprasellar pathologies affected all other patients. Pretreatment thyrotropin (TSH) level (mean +/- standard error of the mean [SEM]) was 2.04 +/- 0.25 mU/L (normal, 0.4-4), and gradually decreased to 0.51 +/- 0.19 mU/L (range, 0.009-3.38) by treatment with levothyroxine in a mean dose of 86 +/- 6 microg/d. TSH was suppressed by thyroid replacement to less than 0.5 mU/L in 80% of patients. Mean baseline free thyroxine (FT4) was 7.55 +/- 0.51 pmol/L (normal, 11.8-24.6) and gradually increased with thyroid hormone to 15.19 +/- 1.0 pmol/L, whereas total thyroxine (TT4) increased from 57.4 +/- 2.6 to 104.4 +/- 5.0 nmol/L (normal, 77-154). Mean pretreatment total triiodothyronine (TT3) was 1.44 +/- 0.09 nmol/L (normal, 1.1-2.7), and was not altered by treatment. Thyrotropin-releasing hormone (TRH) test was performed in 20 patients before thyroid replacement, and mean baseline and peak TSH levels were 1.33 +/- 0.3 and 7.14 +/- 1.62 mU/L, respectively. In 5 subjects TSH was stimulated to 6 mU/L or more, whereas in 5 others TSH was not affected. Based on linear regression of logarithm (Ln) TSH against FT4, a leftward shift of the TSH/FT4 ratio was demonstrated in patients with central hypothyroidism compared to 17 patients with primary hypothyroidism. Plotting measurements of TSH against FT4 for 6 individuals with central hypothyroidism showed different regression slope for each patient. Suppression of TSH by thyroid replacement to levels below 0.1 mU/L predicted euthyroidism in 92% of cases, compared to 34% when TSH was above 1 mU/L (p < 0.0001). In conclusion, in central hypothyroidism baseline TSH is usually within normal values, and is further suppressed by exogenous thyroid hormone as in primary hypothyroidism, but to lower levels. Thus, insufficient replacement may be reflected by inappropriately elevated TSH levels, and may lead to dosage increment.

Insulin-like growth factor-1 (IGF-1) and its binding proteins (IGFBPs) are produced by many tissues and are present in serum and other biological fluids. Alterations in sera of IGF-1 and 2 and IGFBPs were demonstrated in patients with malignancy, infection and other diseases causing pleural effusion. In this study the IGF-1 and IGFBP-2 content and the specific electrophoretic patterns of IGFBPs in samples of sera and pleural effusions of 25 patients with malignancy, infection and congestive heart failure were investigated. IGF-1 levels in exudative effusions of malignant solid tumors were significantly higher [(mean+/-SD), 20.9+/-7.5 nmol/L, n = 9] than in lymphoma (11.0 +/- 5.2 nmol/L, n = 5; p < 0.05), infection (11.4 +/- 6.5 nmol/L, n = 6; p < 0.05) and transudative effusion of congestive heart failure (4.3 +/- 3.3 nmol/L, n = 5; p < 0.02). IGFBP-2 was markedly increased in effusions of malignant solid tumors (2.14 +/- 0.82 mg/L, n = 9) compared with exudates of lymphoma, infection and transudates (1.10 +/- 0.70, 1.22 +/- 0.32 and 0.93 +/- 0.52 nmol/L, respectively, p < 0.05). Moreover, in effusion of solid tumors, IGFBP- 2 levels were higher than those in corresponding sera, which suggests local production of this binding protein. The demonstration of IGFBP- 2 in solid tumor cells by immunohistochemistry further supports this possibility. This work demonstrates the existence of the IGF-1/IGFBP system in pleural fluids from different etiologies and implies possible use of IGF-1 and IGFBP-2 as a potential marker of malignant effusions.

Article Familial Isolated Primary Hyperparathyroidism in a Large Georgian-Jewish Kindred: Genetic Studies was published on April 1, 2001 in the journal International Journal on Disability and Human Development (volume 2, issue 2).

Prolonged furosemide treatment is associated with urinary loss of thiamine and thiamine deficiency in some patients with congestive heart failure and low dietary thiamine intake. In the rat, diuretic-induced thiamine urinary loss is solely dependent on increased diuresis and is unrelated to the type of diuretic used. We studied the effects of single intravenous doses of furosemide (1, 3, and 10 mg) and of normal saline infusion (750 mL) on urinary thiamine excretion in 6 volunteers. Over a 6-hour period, furosemide induced dose-dependent increases in urine flow and sodium excretion rates (mean +/- SD), from 51 +/- 17 mL/h at baseline to 89 +/- 29 mL/h, 110 +/- 38 mL/h, and 183 +/- 58 mL/h (F = 10.4, P < .002) and from 5.1 +/- 2.3 mmol/h to 9.4 +/- 6.8 mmol/h, 12.1 +/- 2.6 mmol/h, and 20.9 +/- 10.6 mmol/h (F = 6.3, P < .005) for the three doses, respectively (104 +/- 35 mL/h and 13.0 +/- 6.2 mmol/h for the saline infusion). During this period the thiamine excretion rate doubled from baseline levels (mean of four 24-hour periods before the diuretic interventions) of 6.4 +/- 5.1 nmol/h to 11.6 +/- 8.2 nmol/h (F = 5.03, P < .01, for all four interventions, no difference being found between them), then returning over the following 18 hours to 6.1 +/- 3.9 nmol/h. The thiamine excretion rate was correlated with the urine flow rate (r = 0.54, P < .001), with no further effect of the type of intervention or sodium excretion rate. These findings complement our previous results in animals and indicate that sustained diuresis of >100 mL/h induces a nonspecific but significant increase in urinary loss of thiamine in human subjects. Thiamine supplements should be considered in patients undergoing sustained diuresis, when dietary deficiency may be present.

Solitary fibrous tumor is an uncommon mesenchymal lesion, seldom associated with hypoglycemia and rarely presents as a perirenal mass. We describe a perirenal solitary fibrous tumor presenting as a renal mass associated with recurrent hypoglycemic events that resolved after nephrectomy. We discuss the diagnosis, endocrine evaluation and mechanism of the associated hypoglycemia of the solitary fibrous tumor.

Long-term furosemide therapy is associated with increased urinary loss of thiamine. To examine the mechanism of furosemide-induced urinary thiamine loss, we measured urinary excretion of thiamine in rats in response to increasing doses of furosemide, acetazolamide, chlorothiazide, amiloride, mannitol, and extracellular fluid (ECF) volume loading by saline infusion. All animals were in normal thiamine balance as reflected by a thiamine pyrophosphate effect (TPPE) of 2.25% +/- 0.60% (mean +/- SEM), and all had normal renal function. Urinary flow increased in response to diuretic administration in a dose-dependent manner, reaching (mean) peak urinary flow rates of 283 to 402 microL/min. Fractional excretion of sodium (FE(Na)) exhibited the same pattern, reaching peak values of 12.3% to 23.2%. Urinary thiamine excretion increased in proportion to the incremental doses of diuretic agents, reaching (mean) maximal values of 7.44 to 9.34 pmol/min, with no significant difference (P = .11) between the various diuretics tested nor in response to saline loading. None of the diuretics tested differed in the effect on thiamine excretion, which was clearly flow dependent and only partially related to fractional sodium excretion. Urinary flow rate, being the single significant predictor, explained 78% (R2 = 0.78) of the variability in thiamine excretion rates. These findings indicate that urinary thiamine loss is caused by a nonspecific, flow-dependent mechanism common to all of the diuretics tested.