Clinical features and therapeutic outcomes of patients with acromegaly: single-center experience.

The aim of this study was to review the outcome of acromegaly treatment, as well as co-morbidity and mortality in a series of patients with acromegaly attending a single center in the last 10 yr. In that period, 53 patients were treated for acromegaly. Transsphenoidal operation was applied as the first-line therapy in 94.3% of patients and it led to disease remission in 59.2% of them. The remission criteria included a nadir GH<1 µg/l after glucose load, and normal age-related IGF-I levels. The remission rate after transsphenoidal surgery was significantly higher in the group of patients with microadenoma (76.9%), than in the group of patients with macroadenoma (52.8%). Patients with invasive tumors had remission rate of 16.7% after transsphenoidal surgery. There were no perioperative deaths. As the second-line treatment somatostatin analogues, radiotherapy, and dopaminergic agonists were used. Hypertension and diabetes were the most frequent co-morbidities in the group of patients. After successful treatment, 30% of patients with diabetes or impaired glucose tolerance had significant improvement of glycemic control. Transsphenoidal surgery is the appropriate firstline therapy in patients with somatotropinoma. Medical and radio-therapy should be reserved as the second-line therapy after surgery failure.

Discriminatory ability of calcaneal quantitative ultrasound in the assessment of bone status in patients with inflammatory bowel disease.

A high incidence of bone disease in patients with inflammatory bowel disease (IBD) requires frequent monitoring of skeletal status and, for that reason, evaluation of radiation-free technology is an issue of interest. Our objective was to appraise the parameters of calcaneal quantitative ultrasound (QUS): broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index (QUI), and establish their t-score values to investigate discriminatory ability of QUS in IBD patients with metabolic bone disease. The study included 126 patients (Crohn's disease [n = 94] and ulcerative colitis [n = 32]), and 228 age- and sex-matched healthy volunteers. Bone status was evaluated on the same day by calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1-L4) and total hip. All QUS measurements were lower in patients compared with healthy controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated significantly but inversely with disease duration (r = -0.3, p = 0.002). There was no difference with respect to type of disease (Crohn's disease or ulcerative colitis) or corticosteroid therapy. All three QUS t-scores were significantly lower in patients who had previously sustained fragile fractures (n = 28) than in those without fracture in their history (n = 98) (t-scores: BUA -2.0 vs. -1.3, p = 0.008; SOS -2.1 vs. -1.4, p = 0.02: QUI -2.3 vs. -1.5, p = 0.009). Axial DXA was not significantly different between the fracture and nonfracture patients (-1.7 vs. -1.2, p = 0.1), whereas total hip DXA showed a discriminatory power between the two (-1.6 vs. -0.7, p = 0.001). Patients with t-score < -1.0 scanned by DXA were classified as bone disease. The sensitivity of QUS to identify bone disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score cutoff

Decreased peak bone mass is associated with a 3-bp deletion/insertion of the CYP19 intron 4 polymorphism: preliminary data from the GOOS study.

Finding that estrogen plays an important role in bone homeostasis in men prompted research on relationship of polymorphism at the CYP19 gene and the bone mass. Therefore, influence of 3-bp deletion/insertion polymorphism of CYP19 (TTTA)7 allele on the peak bone mass attainment in males was studied. Fifty-eight unrelated male participants, aged 21-35, were selected depending on the presence of (TTTA)7 (no.=19) or (TTTA)7-3 (no.=39) alleles from the initial cohort of 92 young males. Heterozygotes (TTTA)7/(TTTA)7-3 (no.=13) were not included in the analysis. Serum levels of estradiol, free testosterone, 25-hydroxyvitamin D, bone alkaline phosphatase, osteocalcin, and beta-crosslaps were measured. Bone mass was measured by DXA at the hip and at the spine. (TTTA)7-3 allele was associated with significantly lower femoral neck bone mineral density (BMD) (p=0.02). Logistic regression model indicated strong association of (TTTA)7-3 allele with low BMD in the range of osteopenia/osteoporosis (p=0.014, odds ratio 12.36, confidence intervals 1.65-92.46). In the present study association of 3-bp deletion polymorphism of the (TTTA)7 allele with decreased peak bone mass in males is reported for the first time. However, further studies are necessary to elucidate the functional relevance of this polymorphism.

Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

Evolution of clinical symptoms in a young woman with a recurrent gonadotroph adenoma causing ovarian hyperstimulation.

OBJECTIVE: To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. PATIENT AND METHODS: Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, beta-LH, inhibin A and B, estradiol, prolactin (PRL), and beta-chorionic gonadotrophin (beta-CG) were measured, and the responses of FSH, LH and beta-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. RESULTS: Enlarged ovaries were found on ultrasound examination simulating a hyperstimulation-like pattern. At that time, elevated levels of FSH (13.4IU/l) and marginally elevated levels of beta-LH (1.43ng/ml) were found, whereas the level of LH (0.5IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150pmol/l). Levels of inhibin A and B were elevated (326pg/ml and 588pg/ml respectively). The prolactin level (70ng/ml) was increased, whereas beta-chorionic gonadotrophin (beta-CG) was normal. Significantly increased FSH, LH, and beta-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for beta-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160pmol/l), whereas basal levels of LH (4.65IU/l) and FSH (3.98IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue confirmed the previous findings. CONCLUSIONS: Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic- to an ovarian hyperstimulation-like pattern during the evolution of the tumour.

Molecular genetics of malignant insulinoma.

Malignant insulinoma is an rare form of cancer with poor prognosis and a reported 5-year survival of 35%. Relatively little is known about the etiology of this disease or of the oncogenes and tumor suppressor genes that participate in its genesis and progression. To address this issue, several protooncogenes, including K-ras, N-ras, erbB-2, erbB-3,c-myc, c-fos, c-jun were examined. Also analyzed was the expression of the growth factors TGF-alpha, EGF, and insulin as well as the EGF receptor (EGF-R), p53 and the putative anti-metastasis gene nm23-H1. These were examined in malignant insulinomas, benign insulinomas, pancreatic B cell hyperplasias and in normal endocrine pancreas. Normal endocrine pancreas showed moderate immunoreaction for c-myc and a strong reaction for insulin. All other parameters were negative. Benign pancreatic B cell hyperplasias were slightly or moderately positive for N-ras and TGF-alpha, and were weakly positive for EGF-R. They were strongly positive for c-myc and insulin. In malignant insulinomas there was strong immunoreaction for c-myc, TGF-alpha, N-ras, K-ras and p53. Insulin reaction was moderate or strong. Molecular genetic studies have been performed for the presence of activating point mutations in codon 12 of the c-K-ras oncogene. Mutations were detected using primer-mediated, mutant-enriched, polymerase chain reaction-restriction fragment length polymorphism analysis and were further characterized by allele-specific oligonucleotide hybridization. Four out of six patients with malignant insulinoma and two out of eight patients with benign insulinoma harbored K-ras point mutations at codon 12. All patients with mutated K-ras oncogene also had elevated levels of p53 protein as well as c-myc and TGF-alpha. In one extremely malignant case we found concomitant mutation at codon 12 of K-ras and codon 61 of the N-ras gene. Our data are consistent with the idea that malignant progression is accompanied by the progressive accumulation of multiple genetic lesions and suggest that activation of myc, TGF-alpha and ras genes may be early events in the development of insulinoma.

Changes of the corrected Q-T interval in the electrocardiogram of patients with anorexia nervosa.

Thirty patients with anorexia nervosa and 30 controls had an electrocardiogram with the corrected Q-T interval. The aim of the study was to analyse the corrected Q-T interval in patients with anorexia nervosa compared with the findings in the control group, to compare the body mass index between two groups and to measure underlying dispersion of the corrected Q-T interval in each of the 12 ECG leads in both groups. All corrected Q-T intervals were measured in each of the 12 ECG leads and the longest values of three consecutive intervals were used for this analysis. The prolonged corrected Q-T interval was found in 12 out of 30 patients with anorexia nervosa (40%), with the longest mean values of 0.421 s (range, 0.334-0.500 s), and in 2 out of 30 patients of the controls (7%), with the longest mean values of 0.390 s (range, 0.343-0.444 s). The difference was statistically significant (t = 4.453, P < 0.001). Relative risk for prolongation of the corrected Q-T interval in patients with anorexia nervosa was high: 12 compared with control subjects. The longest values of the corrected Q-T interval in both groups, and the longest values of the prolonged corrected Q-T interval in both groups were observed in the anteroseptal leads of the electrocardiograms. The mean serum potassium level in the group with anorexia nervosa was 3.97 and in the control group was 4.15 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertebral osteophytosis and vertebral deformities in an elderly population sample.

AIM OF THE STUDY: We investigated the association between vertebral osteophytosis and vertebral deformities in an elderly population sample, and the influence of some risk factors on spinal osteophytosis and deformities. SUBJECTS AND METHODS: A population sample of 280 women and 263 men, all Zagreb residents older than 45 years, participated in the study. Radiographs of the thoracic and lumbar spine were evaluated for the presence of osteophyte formation and vertebral deformities. Osteophyte size was graded on a scale from 0 to 4. Vertebral deformities were determined by the semiquantitative method of McCloskey. The chi-square test was used to analyse the association between vertebral osteophytes and deformities, and the influence of several risk factors was investigated by discriminate analysis. RESULTS: The prevalence of vertebral osteophytosis was 47.9% in men (36.5% in the thoracic and 21.3% in the lumbar spine) and 56.0% in women (36.0% in the thoracic and 23.9% in the lumbar spine). The prevalence of vertebral deformities was 8.3% in men (5.3% in the thoracic and 3.4% in the lumbar spine) and 12.5% in women (7.9% in the thoracic and 5.4% in the lumbar segment). There was a significant association between deformities and osteophytosis on the lumbar segment of the spine (P = 0.0240 men, P = 0.0152 women). Analysing the influence of several risk factors, age was found to be the most associated with both vertebral deformities and osteophytosis. Obesity was significantly associated with osteophytosis. CONCLUSIONS: We found a significant association between vertebral osteophytosis and deformities in the lumbar segment and no relationship in the thoracic segment. This implicates different etiologies of vertebral deformities in the thoracic and lumbar spine.

Diagnostic value of thyrotropin releasing hormone test in 129 patients with suspected tumoral hyperprolactinemia.

In 129 hyperprolactinemic (PRL > or = 100 ng/mL) and 100 normoprolactinemic patients (PRL 0-25 ng/mL), delta max. PRL (the difference between maximal prolactin (PRL) after thyrotropin releasing hormone (TRH) injection and basal value) was compared with basal PRL and computed tomography (CT) of the sellar region. In 122 hyperprolactinemic patients delta max. PRL was < 100%, while tumor was found in 106 of them. In the remainder seven hyperprolactinemic patients delta max. PRL was > or = 100% and CT showed no tumor. A significant difference in delta max. PRL between hyperprolactinemic patients without and those with verified adenoma was found and showed a significant negative correlation with basal PRL. Between 122 hyperprolactinemic patients with delta max. PRL < 100%, mean basal PRL and duration of clinical symptoms were significantly lower in 16 patients with normal CT compared to 106 patients with tumor. All normoprolactinemic patients showed delta max. PRL > or = 100% and no tumor on CT. PRL stimulation disturbance precedes tumor visualization and represents a decisive diagnostic parameter in hyperprolactinemic patients with no tumor signs.

Effects of combined treatment with etidronate, nandrolone-decanoate and calcium on bone mineral density in postmenopausal women.

The objective of this retrospective study was to see whether the effect on bone mineral density (BMD) and response to the intermittent cyclic treatment with etidronate (E) + nandrolone-decanoate (ND + calcium (Ca) (group A--combined regimen--400 mg E daily for 2 weeks, followed by 500 mg Ca daily for the next 10 weeks + 50 mg ND once a month i.m., for 3 months in every other E cycle) was of greater benefit than cyclic E + Ca treatment (group B--standard regimen--E + Ca given in the same manner as in group A) or Ca treatment alone (group C--calcium regimen--500 mg Ca daily, continuously for 1 year). Group A comprised 30, group B 27 and group C 26 postmenopausal women with spinal BMD > or = 1 standard deviation below young adult mean (T score < or = -1) without vertebral fractures. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck before (baseline values) and after one year treatment period. A similar, statistically significant increase in BMD was noted at lumbar spine in groups A and B (3.6% and 3.8%, respectively) and at femoral neck in groups A and B (1.7% and 2.5%, respectively). In group C, the bone loss at lumbar spine was prevented but no significant increase was recorded (0.3%) and at femoral neck an insignificant decrease in BMD was recorded (-0.3%). Percentages of change from baseline were significantly higher in groups A and B in respect to those in group C but there were no significant differences between groups A and B either at lumbar spine or at femoral neck. In about 30% of women from groups A and B, spinal BMD increased by more than 4.2% ("real" responders to the given therapy). A femoral BMD increase of more than 5.6% was recorded in about 13% of women from groups A and B. In group C, no such increase was recorded. In conclusion, combined intermittent cyclical regimen of E + ND + Ca has not proven to be superior to the intermittent cyclic regimen of E + Ca.

[Clinical significance of testosterone and dihydrotestosterone metabolism in women]. / Klinicko znacenje metabolizma testosterona i dihidrotestosterona u zena.

Hyperandrogenism in women refers to both excess androgen production and clinical manifestations of androgen excess. Clinical evaluation of women with hyperandrogenism is complex. The synthesis and release of androgenic steroid in women are normal part of adrenal and ovarian steroidogenesis. One of the classic questions concerning androgenic disorders concerns the source of circulating androgens. Relative roles of adrenal and ovary vary greatly, both can be involved. The use of gonadal or adrenal steroid administration can sometimes be used to distinguish the source of androgen excess. In many cases of hyperandrogenism no laboratory diagnosis of adrenal and ovarian androgen overproduction can be made. These patients may have increased androgen sensitivity due to increased enzyme 5 alpha-reductase activity in the skin. To be active in the skin, testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5 alpha-reductase. The increase in DHT production is a localized phenomenon and there is no generalized increase in enzyme activity in women with hyperandrogenism. DHT is rapidly converted to other steroid metabolites including androsteron, androstanediol and their glucuronide and sulfate conjugates. Although once thought to be specific for skin conversion of T to DTH these androgen conjugates reflect adrenal steroid production and metabolism. Antiandrogens (androgen receptor blockers) are the most effective therapeutic modalities of cutaneous hyperandrogenism. Clinical trials are in progress to determine efficacy of finasteride for the treatment of hirsutism and androgenetic alopecia. Finasteride is the first available medication of a new class of drugs that is an competitive inhibitor of 5 alpha-reductase and therefore should be beneficial for medical treatment of cutaneous hyperandrogenism.

[Epidemiology, classification and clinical aspects of hyperandrogenemia]. / Epidemiologija, klasifikacija, klinicka slika hiperandrogenemije.

Hyperandogenemia in women is manifested typically by clinical features that may include hirsutism, acne, central obesity, male pattern baldness, increased waist-to-hip ratio, clitoral hypertrophy and deepening of the voice. The differential diagnosis include Cushing syndrome, PCO and iatrogenic hirsutism. Complications include cardiovascular disease, intravascular disease and insulin resistance. An interdisciplinary approach to management is strongly recommended. Risk reduction strategies include correction of dyslipidemias, low-dose aspirin for primary prevention of myocardial infarction, maintenance of ideal weight, smoking cessation, use of oral contraceptives with low progestin, and postmenopausal estrogen replacement.

[Arterial hypertension in the obese--aspects of etiopathogenesis]. / Arterijska hipertenzija pretilih--pogled na etiopatogenezu.

Many epidemiological and clinical studies show a strong association between arterial hypertension and obesity. The underlying pathophysiological mechanism is unknown. It is thought that the etiopathogenesis of obesity hypertension is exceptional and in that view hormonal, neural, volume and hemodynamic properties of obesity, as well as salt and/or caloric consumption, are outlined. In this article all these factors are discussed. According to the current hypothesis, hyperinsulinemia which is probably a physiologic adaptation to obesity, plays a key role in the pathogenesis of arterial hypertension. Insulin increases the reabsorption of sodium by means of an immediate effect on the kidney tubules. An increase of sodium in the body leads to hypervolemia and to the elevated blood pressure. Chronic hyperinsulinemia perhaps increases the blood pressure indirectly also by means of the central nervous system, namely, by stimulating the activity of the sympathetics.

[Tonometry in the diagnosis of subclinical ophthalmopathy in patients with Basedow's disease]. / Tonometrija u dijagnostici supklinicke oftalmopatije u bolesnika s Basedowljevom bolesti.

Ophthalmopathy in addition to hyperthyreosis with goitre and dermopathy is characteristic of Basedow's exophthalmos is frequently associated with elevated intraocular pressure (IOP) on upgaze. We wanted to examine whether these changes of IOP exist in patients with Basedow's disease without clinical manifestations of ophthalmopathy. We measured IOP with Goldmann's applanation tonometry in two positions: the primary position, when the patient looks straight ahead and then on upgaze. Forty-six patients with Basedow's disease were examined. The minority [5 (11%)] of the 46 patients had exophthalmos and 22 (47%) of them had abnormal IOP (delta IOP greater than or equal to 3 mmHg). The average interval between the onset of Basedow's disease and this study was 12.8 +/- 7.4 years for those patients who had exaggerated positional changes in IOP, as compared with 5.8 +/- 3.3 years for those with normal IOP, P less than 0.01. We conclude that Basedow's ophthalmopathy is more common than is recognized clinically and that ophthalmopathy is more frequent in patients suffering of Basedow's disease for a longer period. Measuring IOP in two positions is a very simple method which could help us in early diagnosis of ophthalmopathy in patients with Basedow's disease.

[Metabolic diseases and the high-fiber diet]. / Metabolicke bolesti i prehrana obogacena vlaknima.

There is no doubt that fiber, in particular viscous dietary fiber, has a positive effect on human health both in the prevention and treatment of chronic diseases. Over 30 years of intensive clinical research with guar, psyllium, oat and other fiber-rich foods has repeatedly demonstrated the health benefits of dietary fiber in lowering insulin requirements and improving blood glucose control in diabetics, as well as reducing serum lipid levels in hyperlipidemics. Accumulating epidemiological evidence is also supporting the link between high-fiber diets and the reduction of risk for heart disease and cancer. As a result, increased dietary fiber is recommended by health authorities worldwide. However, the mechanism of fibers' action is not fully understood and the effect is not always consistent with the expected results. One of the reasons could be the large intra- and inter-fiber variability due to its complex structural and physicochemical characteristics. As a consequence, some of the health agencies focus their recommendations more on the type of dietary fat rather than a high carbohydrate/high-fiber.

[The role of the TRS-Glucotest apparatus in self-monitoring by patients with diabetes mellitus]. / Uloga TRS-Glukotest aparata u samokontroli bolesnika sa secernom bolesti.

Successful treatment of diabetes mellitus requires a reliable control of glycaemia where self-monitoring with reflectometer plays a significant role. TRS-glucotest reflectometer (TRS, Zagreb), the result of our experts' efforts, makes it possible for diabetic patients to perform self-monitoring. According to our research TRS-glucotest reflectometer shows lower blood glucose levels for more than 20%, especially in 3.8-11.5 mmol/L range of glucose concentration, that is in the range most often expected in patients with diabetes got under control. A considerable dispersion of the results got by measuring glucose levels with reflectometer doesn't offer the possibility to correct the obtained values. Our results suggest that TRS-glucotest reflectometer should be improved so that reliable control of glycaemia can be made what is especially important in patients with intensive conventional insulin treatment.

[Turner's syndrome--case report of a female patient with chromosome mosaicism]. / Turnerov sindrom--prikaz bolesnice s kromosomskim mozaicizmom.

A 45-year old woman with the typical Turner's phenotype (short stature, short and broad neck, shield chest and low hairline) and signs of ovarian failure started at the age of 37 with menopause at the age of 44, is presented. The cytogenetic analysis showed the presence of three different cell lines with 45,X, 46,XX and 47,XXX karyotypes. It is a rare type of mosaicism, combining Turner's and triple-X syndrome. Interestingly, the became pregnant and gave birth to a healthy child. Second pregnancy resulted in a miscarriage in the first trimester.

[Corrected Q-T interval in the electrocardiogram in patients with anorexia nervosa]. / Korigirani Q-T interval u elektrokardiogramu u bolesnika s anoreksijom nervozom.

This paper examined the corrected Q-T interval in a group of 15 patients with anorexia nervosa and in 30 patients of a control group. Prolonged corrected Q-T interval was found in 2 of 15 patients with anorexia nervosa (13%) and in one of 30 patients of a control group (3%). The correlation between corrected Q-T interval and body mass index in patients with anorexia nervosa was not found (r = +0.13). Relative risk for prolonged corrected Q-T interval in patients with anorexia nervosa was high (4.5) compared with a control group. It is well known that prolonged corrected Q-T interval is connected with a high risk for sudden death because of a malignant ventricular arrhythmias.

[Bone mineral density in patients on long-term therapy with levothyroxine]. / Mineralna gustoca kosti u bolesnica na dugotrajnoj terapiji levotiroksinom.

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.