Comparison of orlistat and sibutramine in an obesity management program: efficacy, compliance, and weight regain after noncompliance.

To describe the comparative efficacy of orlistat and sibutramine in an obesity management program, with specific attention to compliance and weight regains after noncompliance. We prospectively evaluated 182 obese patients who were randomized to treatment with orlistat (n=98) or sibutramine (n=84) along with the diet and exercise prescriptions. Compliance (or compliant patient) was defined as adherence to scheduled visit times (at 3- month intervals) and following the prescribed drug regimen. A telephone survey was conducted in case of noncompliance. Significant body weights improvements were seen in both treatment groups. Patients lost a mean of 7.6+/-2.8% and 10.5+/-2.9% of initial body weights after a mean drug use of 8.8+/-5.7 and 8.3+/-3.7 months in the orlistat and sibutramine groups, respectively (p<0.05 vs. initial body weight). Patients in the sibutramine group lost more weight than the orlistat group (p<0.05). A total of 102 patients (56%) were compliant (53.1% in the orlistat group and 59.5% in the sibutramine group). Factors associated with compliance included weight reduction of more than 5% in the first 3 months and adherence to physical activity. Higher initial body weight, prior anti-obesity therapy, number of concurrent medications, and comorbidity were associated with noncompliance. Weight regains in noncompliant patient were a mean of 5.2+/-5.1 kg after a mean period of 9.2+/-4.2 months in the orlistat group, and a mean of 6.1+/-3.8 kg after a mean period of 9.1+/-3.9 months in the sibutramine group (p<0.05 vs. last visit for both groups, p>0.05 between groups). Both drugs in an obesity management program can achieve substantial weight loss. However, noncompliance and rebound weight regain after noncompliance are considerable problems.

Suppressive therapy with levothyroxine for euthyroid diffuse and nodular goiter.

In this study, 35 patients with euthyroid diffuse goiter and 35 patients with euthyroid nodular goiter were treated with Levothyroxine (L-T4) for six months. The aim was to evaluate the efficacy of treatment on thyroid and nodule volumes and to evaluate the correlation between volume changes and thyroglobulin levels. Serum thyroid hormones, TSH, thyroglobulin, thyroid and nodule volumes were measured at the initial visit and after 6 months. Radioactive iodine uptakes of the thyroid gland were evaluated before treatment. The mean decrease of thyroid volume at six months was about 20% (20.4 +/- 8.8 ml vs. 16 +/- 7.9 ml, P<0.001) in patients with diffuse goiter. All patients with diffuse goiter showed some decrement in their goiter sizes. Thyroid nodules, in response to thyroid hormone treatment, showed a variable behavior. A reduction of 50% or more in volume was detected in 31% (11/35) of the patients. 54% of the patients (19/35) showed a 10-49% decrease in nodule volume. Five of the patients were found to be insensitive to the therapy. Their nodule volumes either increased or did not change during therapy. Free T4 and free T3 levels increased and TSH levels decreased with L-T4 treatment in all patient groups. Patients with higher TSH levels (within normal limits) showed more volume reduction in the diffuse goiter group. No uniform correlation was found between volume changes and thyroglobulin levels in either of the patient groups. In conclusion, suppressive thyroxine treatment is effective in reducing the size of the goiter, and nodules and thyroglobulin levels cannot be taken as an indicator of the efficacy of L-T4 therapy.

Degree of thyrotropin suppression in differentiated thyroid cancer without recurrence or metastases.

Forty-eight patients with differentiated thyroid cancer (DTC), who had no evidence of tumor recurrence or metastases on studies such as radioiodine scanning, neck ultrasonography, and with thyrotropin (TSH) and thyroglobulin (Tg) levels less than 1 mU/L and 5 ng/mL, respectively, were included in the study. The mean age was 43 +/- 12 years (range 15-65) and all were receiving levothyroxine (LT4) treatment with a mean dose of 184 +/- 46 microg daily. Patients were divided into two groups; group A included patients that had baseline TSH levels of 0.4 mU/L or more, and group B patients had baseline TSH levels of less than 0.4 mU/L. LT4 doses for all patients were increased, and serum TSH and Tg measurements were reevaluated after 2 months of dose increments. The mean TSH of group A (patients with baseline TSH levels > or = 0.4 mU/L) decreased from 0.67 +/- 0.28 mU/L to 0.16 +/- 0.08 mU/L (p < 0.001), but mean serum Tg level showed no change after dose increments (2.92 +/- 1.36 ng/mL vs. 3.59 +/- 0.93 ng/mL at the second month; p > 0.05). Similar results were also observed in group B (patients with baseline TSH levels < 0.4 mU/L). Mean TSH level decreased from 0.26 +/- 0.07 mU/L to 0.1 +/- 0.05 mU/L (p = 0.006), but no decrease occurred in mean Tg level (3.0 +/- 1.16 ng/mL vs. 3.3 +/- 1.03 ng/mL; p > 0.05). The patients' data were reevaluated according to second-month TSH levels. Patients with a TSH level between 0.11 to 0.4 mU/L were set as "final TSH > 0.1 group," and patients with a TSH level equal or less than 0.1 mU/L were set as "final TSH < or = 0.1 group," and baseline and second-month Tg levels were assessed. The mean second month Tg levels did not differ in these two patient groups (3.7 +/- 0.74 ng/mL for final TSH > 0.1 group vs. 3.3 +/- 1.2 ng/mL for final TSH < or = 0.1 group; p > 0.05). No difference could be found between initial and second-month Tg levels in both groups (2.8 +/- 1.4 ng/mL vs. 3.7 +/- 0.74 ng/mL in final TSH > 0.1 group and 3.11 +/- 1.1 ng/mL vs. 3.3 +/- 1.2 in final TSH < or = 0.1 group; p > 0.05). In conclusion, these results indicate that serum Tg levels cannot be suppressed by maximal TSH suppression in tumor-free DTC patients. The suppression of TSH to less than 0.1 mU/L seems not to be necessary in most patients who have no evidence of active disease.

Value of re-aspirations in benign nodular thyroid disease.

Fine-needle aspiration cytology (FNAC) is the most useful procedure for the evaluation of thyroid nodules. The requirement for repeated aspirations in the follow-up of benign nodular thyroid disease, however, is controversial. To determine the value of re-aspirations in benign nodular thyroid disease, we studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19 male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151) thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46 were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407 (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change after multiple aspirations in 213 (98.61%) of the cases. Three patients with initial aspirations read as benign had a diagnosis of PC from their second biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC revealed atypical features in 1 of the 3 patients. These 3 patients likely represent a false-negative result of the initial FNAC rather than benign nodular disease transformed to a malignant one during the follow-up period. In conclusion, a second aspiration of clinically suspicious nodules may correct a few initial false-negative results, but routine additional re-aspirations are not useful for clinically stable disease.

A potential risk for osteomalacia due to sociocultural lifestyle in Turkish women.

Osteomalacia is a metabolic bone disease caused by deficiency of vitamin D or its active metabolites. Because poor sunlight exposure is one of the most common causes of osteomalacia, the disease seems to be rare in countries with adequate sunlight. We report nine Turkish female patients with osteomalacia with ages between 21 and 50 years. Osteomalacia was diagnosed on the basis of a history of bone aches or pains, muscle weakness, low or low normal serum calcium and urinary calcium, decreased concentrations of serum inorganic phosphorus and 25- hydroxyvitamin D and increased serum intact PTH and alkaline phosphatase levels. Radiographically, pseudo-fractures were present in seven of the patients. The patients' symptoms and signs were relieved with the treatment with vitamin D analogues and calcium. Their hypovitaminosis D are suggested to be caused by excessive clothing in the outdoors due to sociocultural and religious reasons. Excessive clothing may be a risk factor for osteomalacia in young to middle-aged and otherwise healthy women even in countries with adequate sunlight.

Omeprazole: calcitonin stimulation test for the diagnosis follow-up and family screening in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) occurs sporadically but may also be inherited as part of the multiple endocrine neoplasia (MEN) type 2 syndrome. Screening of the patients and first degree relatives annually with basal and provocative tests for serum immunoreactive calcitonin (CT) levels is essential and enables potentially curative disease. Pentagastrin and calcium are the usual provocative agents used worldwide. We used endogenous gastrin (GT) release achieved by omeprazole, 20 mg b.i.d., to stimulate CT in 9 MTC, in 3 MEN 2A family members, and in 50 healthy control subjects. A steady and significant increase both in GT and CT levels was achieved in 9 MTC patients and 3 of the 14 family members tested, whereas in healthy controls the CT increase stimulated by GT was insignificant. Preliminary results showed that this new, safe, cheap, and outpatient-basis test can be used in MTC diagnosis, follow-up, and screening.

Non-Hodgkin's lymphoma presenting as thyroid and adrenal gland involvement.

We report an unusual case of non-Hodgkin's lymphoma involving both the thyroid and adrenal glands. Malignant infiltration of the glands by B-cell immunoblastic type lymphoma were demonstrated by cytologic findings in needle biopsy. Staging studies showed minor nodal involvement. The patient was treated with combination chemotherapy. Simultaneous involvement of the thyroid and adrenal glands with non-Hodgkin's lymphoma is very rare. In this report, while presenting this rare coexistence, we also want to emphasize that fine-needle aspiration biopsy was useful in the diagnosis.

Obesity and left ventricular diastolic dysfunction.

To assess the influence of obesity on left ventricular function, 20 obese women (mean body mass index (BMI) 33.8 +/- 3.1 kg/m2 and mean age 31.1 +/- 2.4 years) without evidence of heart disease were evaluated by echocardiography. Obese subjects had greater left ventricular mass index (103 +/- 22 g/m2, 76 +/- 18 g/m2; P < 0.0001) and augmented fractional shortening (39 +/- 2.6%, 36 +/- 0.1%; P < 0.0001) than normals. Isovolumic relaxation time was prolonged in the obese group (92 +/- 11 ms) as compared with the control group (76 +/- 11 ms; P < 0.0001). The ratio of peak early and atrial filling velocities was significantly lower (1.2 +/- 0.4, 1.9 +/- 0.6; P < 0.0001) and atrial contribution was higher (39 +/- 9, 25 +/- 5; P < 0.0001) in obese subjects than in normals. Shortened deceleration time was measured in obese subjects (142 +/- 30, 179 +/- 20 ms; P < 0.0001). In conclusion, obesity causes relaxation and early filling abnormalities and diastolic filling is compensated by augmented atrial contribution. Diastolic dysfunction is an early indicator of cardiac involvement in obesity.

The characteristics of nine patients with adrenal incidentalomas.

With the widening use of computerized tomography, the incidentaloma, an adenoma found incidentally in the adrenal, in computerized tomograms obtained for problems not necessarily related to the adrenal, has emerged as a recent clinical entity. Nine cases with such tumors are presented, here, along with a brief review of the related medical literature. Endocrine and other studies have shown that two of these nine patients had hormone secreting adrenal tumors, two pheochromocytomas. Surgical resection of the tumor was performed in six of the cases and aspiration biopsy was done in four with three completely benign cytological examination results (Class I or II) and one Class III result. The tumor with the class III result turned out to be a benign pheochromocytoma. CT estimates of the tumor size were 25 mm to 80 mm in the whole group and 30 to 80 mm in the patients who were operated on. Operation and histopathologic examination revealed three cortical adenomas, two pheochromocytomas, and one myelolipoma. Although no malignant tumors were found, the percentage of functioning adrenal neoplasms is rather high (22.2%) in this group of nine incidentalomas. Cases of adrenal incidentaloma therefore require a thorough endocrine evaluation along with other examinations which allow the clinician to follow tumor size.

Normal growth and pubertal development during bromocriptine therapy in two patients with prolactinoma.

The cases of two boys, a 14 years 10 months old and an 18-year-old, with delayed puberty are presented. The first patient also had a short stature. Both patients had a pituitary adenoma, as shown by computed tomography, with high prolactin levels. After bromocriptine therapy was started, there was a spontaneous progression of normal puberty. The first patient used a synthetic growth hormone together with bromocriptine, however, even after the growth hormone was stopped progression in puberty and gain in height continued. The favorable response obtained in these patients implies that bromocriptine can be an effective therapy for adolescent patients with prolactinoma.

The use of antiandrogen flutamide in the treatment of hirsutism.

In this study the efficacy of flutamide, an antiandrogen which does not have a steroid structure, or progestational and estrogenic activities, on hirsutism and hormone levels in polycystic ovary syndrome (PCOS) and idiopathic hirsutism (IH) was investigated. Ten patients with PCOS and nine patients with IH between 19 and 36 years of age were selected for the study. They were given a 500 mg daily dose of flutamide and were followed up for clinical and hormonal effects at the second, sixth, eighth and twelfth months of the treatment. The severity of hirsutism was assessed according to the Ferriman-Gallwey's score. There was a slight decrease to below the pre-treatment level in serum LH at the end of the eighth month (P < 0.05) and there was also a persistent decrease in progesterone (P) after the second month of the treatment (P < 0.05). No other significant change was observed in ovarian or adrenal androgens. Clinical examinations revealed that after six months of the therapy the dose of flutamide had caused a significant alleviation of hirsutism and this continued during the following months.

Adrenal autotransplantation after total adrenalectomy: delayed determined function.

Adrenal autotransplantation after bilateral total adrenalectomy has been utilized to eliminate the need for replacement therapy and to prevent the late occurrence of Nelson's syndrome in some patients with Cushing's disease. It is possible to follow these cases up closely today, owing to the highly developed hormonal evaluation and imaging techniques. In this study, two patients who underwent bilateral total adrenalectomy and cortex autotransplantation are presented. The autografts were found functional and the patients had not required any steroid replacement therapy.

Localized non-Hodgkin's lymphoma of the adrenal and thyroid glands.

A case of immunoblastic lymphoma, involving only the thyroid and the adrenal glands, is presented. The patient had clinical symptoms and findings of Addison's disease, and computed tomography (CT) demonstrated bilateral adrenal tumoral enlargement. He also had euthyroid diffuse multinodular goiter. The diagnosis of the patient was based on the cytological examination of the aspiration materials from both endocrine glands. The patient received "m-BNCOD" chemotherapy regimen and replacement therapy for Addison's disease. At the end of three courses, a partial response was obtained.

Hirsutism due to the treatment with L-thyroxine in patients with thyroid pathology.

There are many factors involved in the aetiology of hirsutism. It is well known that some drugs may cause hirsutism as a side effect, such as phenytoin, diazoxide, minoxidil etc. In Turkey, where the endemic goiter constitutes an important health problem, the value of suppression therapy with thyroid hormone still carries a special importance. We established the increasing tendency of hirsutism in patients treated with L-thyroxine (L-T4) for various thyroid pathology. That is why we decided to evaluate the role of thyroid hormones in the aetiology of hirsutism observed in patients treated with L-T4. We determined the total and free T3, T4, TSH, TBG, Plasma Cortisol transcortin, delta-4-androstenedione, FSH, LH, prolactin, total and free testosterone, estradiol, progesterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and 17 hydroxyprogesterone (17 OH Pg) levels in serum or plasma in a group of female patients who were taking L-T4 daily, regularly at least for 6 months and complaining of the occurrence of hirsutism. We demonstrated in these patients SHBG, transcortin and estradiol levels significantly lower than controls (p less than 0.001, p less than 0.05 and p less than 0.05, respectively) and DHEAS level significantly higher than controls (p less than 0.001). An important correlation was found between TBG and SHBG levels (r:0.536, p less than 0.05) and also between total and free testosterone levels (r:0.952, p less than 0.001).

Asymptomatic-nonfunctional adrenal masses detected by CT.

We identified as an incidental finding "silent adrenal tumors" in 12 patients undergoing abdominal computed tomography (CT) scanning for unrelated problems. Until recently, adrenal masses came to clinical attention either from local symptoms due to massive enlargement or from manifestations of excess hormone production. With CT, small adrenal glands and neoplasms could be also visualized and diagnosed at an earlier preclinical stage. Patients with asymptomatic adrenal masses detected by CT scan must be investigated for the possibility of metastasis from another primary site, secondly screened for hormone production and should be followed-up for malignant degeneration. The investigation did not show any sound criteria for the diagnosis of malignancy except the follow-up of the masses with serial CT scans in short intervals.

The value of L-thyroxine in the supressive therapy of euthyroid nodules and in the prevention of post-thyroidectomy recurrences.

Long-term L-thyroxine (L-T4) suppression therapy was applied to 133 patients with euthyroid nodular goiter (126 females/7 males) and to 148 patients (136 females/12 males) with post-thyroidectomy recurrence between the years 1980 and 1986. The results are interpreted as "Complete Success" if the nodule disappeared, "Partial Success" if it became smaller, "Late Unresponsiveness" if the nodule first decreased then increased in volume and "Unresponsiveness" when it did not change. In the group of euthyroid nodules, complete success was obtained with 150-200 micrograms/L-T4 daily administration. But in the recurrence group the response to the same dose was lower than in the first group and most of them were partial responders. On the other hand, we found highly significant differences in the incidence of postoperative recurrences, between the group of patients subjected to a long term L-T4 suppression therapy with the recurrence and prophylactic therapy with L-T4. While postoperative recurrence was only 6.35% in the long term L-T4 receiving group, it was very high (80.95%) in the non-treated group. Furthermore, in the group of patients taking L-T4 suppression therapy only for a short period, the incidence of recurrence was 12.70%. As a result of this study, we concluded that routine long term L-T4 suppression therapy is necessary both for the treatment of selected euthyroid nodules without any suspicion of malignancy for the prevention of post-thyroidectomy recurrences.