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In this study, we compared the efficacy of a dipeptidyl peptidase-4 inhibitor (DPP4i) to improve glucose control in patients with type 2 diabetes mellitus (T2DM) with or without Hashimoto's thyroiditis (HT). First, we compared the change in glycated hemoglobin (HbA1c) between the hypothyroid condition (before levothyroxine sodium hydrate [LT4] treatment) and euthyroid condition (after LT4 treatment when patients had achieved euthyroidism for at least six months) in patients with T2DM and HT. Next, we compared the change in HbA1c levels before and six months of DPP4i treatment in patients with T2DM with and without HT. In hypothyroid condition the change in HbA1c after six months of DPP4i treatment was 0.13% ± 0.86%. The change in HbA1c levels from when patients first achieved euthyroidism to after six months in the euthyroid condition was 0.26% ± 0.90%. DPP4i efficacy in patients with T2DM and HT was reduced compared to patients with T2DM but without HT (-0.40 ± 0.90 vs. -0.99 ± 0.5, p = 0.0032). These data suggest that hypothyroidism does not impact on DPP4i efficacy. However, the effect of DPP4i in patients with T2DM and HT was reduced compared to that in T2DM patients without HT. An estimation of thyroid function before prescribing DPP4i may be useful tool for predicting the efficacy of DPP4i, allowing the ruling out complications from HT.

Iodine deficiency affects people of all age groups and yields detrimental health effects known as Iodine Deficiency Disorders (IDD). Universal Salt Iodization (USI) where above 90% household use iodized salt became the main program to optimized population iodine status. This study aimed to analyze iodine in salt, iodine status and thyroid functions from three different IDD endemic regions. Methods This was a cross-sectional study, with women of reproductive age (15 to 45 y old) as subjects, conducted in plain area (Yogyakarta) city (n=250), mountainous area (Bukit Tinggi city) (n=249), and combination of mountaneous and plain area (Purworejo regency) (n=249). Urinary iodine (UIE), prevalence of hyperthyroidism, and hypothyroidism (diagnostic based on combination of TSH and fT4 level), also the presence or absence and level of iodine in salt were assessed. Result Iodized salt coverage have reached >90% household in all three region, while titration found 75.6% with adequate level of iodine in salt (>30 ppm), with wide range of iodine level in salt (0.00-218.2 ppm). With that condition, population in plain and combination of plain and mountainous area have more than adequate iodine status (218 μg/L and 224 μg/L), while population in mountaneous area still in mild iodine deficiency status (UIE median of 88 μg/L). Most population is in euthyroid condition. Hyperthyroidism, subclinical hyperthyroidism, secondary hyperthyroidism, subclinical hypothyroidism, and hypothyroidism were found in 0.7%, 4.8%, 0.4%, 8.9%, and 0.9% population consecutively. There were no relationship between iodine status and prevalence of hyperthyroidism and hypothyroidism, but subclinical hypothyroidism most prevalent in excess UIE population (12.5% vs 8.3%). Conclusion All three regions have achieved USI target. But the risk of iodine deficiency still found in mountaneous area. Household iodized salt coverage discrepancy between rapid test and titration strengthen the need of more accurate but efficient test of iodine level in salt.

Previous reports by us and other investigators showed that among athyreotic patients on levothyroxine (LT4) following total thyroidectomy patients with normal serum thyroid-stimulating hormone (TSH) levels had mildly low serum free triiodothyronine (FT3) levels, whereas patients with mildly suppressed serum TSH levels had normal serum FT3 levels and patients with strongly suppressed serum TSH had elevated serum FT3 levels. The objective of this study was to clarify which of these three patient groups are closer to their preoperative euthyroid condition based on reported subjective symptoms. We prospectively studied 148 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy. Symptoms reflecting thyroid function documented preoperatively and following 12 months of LT4 after thyroidectomy were compared. In 65 patients with strongly suppressed TSH levels significant changes in symptoms with tendencies towards thyrotoxicosis were seen with regards to heat and cold tolerance (p < 0.01), bowel movements (p < 0.05), and hand tremors (p < 0.05). In 33 patients with normal TSH levels, significant changes in symptoms with tendencies towards hypothyroidism were seen with regards to heat and cold tolerance (p < 0.05) and activity (p < 0.05). Lastly, in 50 patients with mildly suppressed TSH levels and FT3 levels equivalent to preoperative levels, all symptom items remained equivalent to their preoperative levels. Symptoms reflecting thyroid function in patients on LT4 following total thyroidectomy suggested that patients with mildly suppressed TSH levels were closest to a euthyroid status. These data provide useful findings regarding the management of patients following total thyroidectomy.

Background: Some investigators reported that among athyreotic patients on levothyroxine (LT4) monotherapy following total thyroidectomy, the patients with normal serum thyrotropin (TSH) levels had mildly low serum free triiodothyronine (fT3) levels, whereas the patients with mildly suppressed serum TSH levels had normal serum fT3 levels, and the patients with strongly suppressed serum TSH had elevated serum fT3 levels. The objective of the present study was to clarify which of these three patient groups is closer to their preoperative euthyroid condition. Methods: A total of 133 consecutive euthyroid patients with papillary thyroid carcinoma who underwent a total thyroidectomy were prospectively studied. The patients' serum levels of lipoproteins, sex hormone-binding globulin, and bone metabolic markers measured preoperatively were compared with the levels measured at postoperative LT4 therapy 12 months after the thyroidectomy. Results: The postoperative serum sex hormone-binding globulin (p

Introduction: A good number of hyperthyroid patients may show delayed recovery of Thyroid Stimulating Hormone (TSH) level in clinically evident euthyroid condition after radioiodine therapy. This group of patients need to be addressed in therapeutic decision making. The purpose of the study was to evaluate the duration and pattern of lag in TSH recovery after I - 131 therapy and the relationship between clinical parameters with stable thyroid function status.Materials and Methods: Total 192 hyperthyroid patients treated with I-131 were included in this study. These patients were followed up clinically and biochemically at three month, six month and one year after radioiodine therapy. Patients having suppressed TSH with normal Free Triiodothyronine (FT3) / Free Thyroxin (FT4) level and clinically euthyroid condition were followed-up for one year without giving antithyroid drug.Results: At three months follow-up 42/192 (22%) had suppressed TSH with normal FT3/FT4 level. Duration of lagging behind state of TSH was three months for 42 patients (22 %), six months for 13 patients (7%) and One year in three patients (2 %). Twelve patients were lost from follow-up. Among 30 patients with lag behind TSH level, 16 (53%) became hypothyroid, 8 (27%) became euthyroid and 6 (20%) became hyperthyroid at one year follow-up. Lagging behind patient with high serum FT4 level at diagnosis and high Radio Active Iodine Uptake (RAIU) showed increased rate of relapse of hyperthyroidism.Conclusion: Lagging state of TSH may be unexpectedly prolonged in some hyperthyroid patients treated with I-131. These patients should be followed up with both TSH and thyroid hormone levels. Most of them do not require further therapy with short period of time.Bangladesh J. Nuclear Med. 17(2): 103-107, July 2014

Purpose. To analyze the association between hypothyroidism and keratoconus, we examined blood thyroid hormone levels and corneal tomographic parameters in healthy subjects and patients with keratoconus.Methods. We included 626 subjects (304 left eyes, 49%; 431 males, 69%; age 38.4 ± 14.3 y). Patients with keratoconus were from our Homburg Keratoconus Center (HKC) (n = 463); patients with hypothyroidism were from the Department of Internal Medicine of Saarland Medical University, Homburg/Saar, Germany (n = 75); and healthy subjects were from the Department of Ophthalmology of Saarland University Medical Center (n = 88). We included only one randomly selected eye of each subject and the first examination data.Exclusion criteria.Previous thyroid medication, previous ocular surgery, and patients with suspected keratoconus (topographic keratoconus classification, [TKC]: 0 Results. The significance levels for a constant parameter, sex, thyroid condition, and age werep<0.0001,p<0.0001,p<0.0001, andp=0.003, respectively. The odds ratios for age, sex, and hypothyroidism were 0.98, 3.05, and 3.34, respectively. Male sex and a euthyroid condition had significantly positive, clinically relevant effects, and age had a significantly negative, but clinically irrelevant effect on the estimated TKC index.Conclusions. Keratoconus appeared to occur more often in patients classified as euthyroid than in patients with hypothyroidism. Thus, hypothyroidism alone could not support the development of keratoconus. Based on these results, it should not be mandatory to screen patients with hypothyroidism for keratoconus or patients with keratoconus for hypothyroidism.

The research of macro - and microelements in uterus, placenta and umbilical cord at the pregnancy on background of pathology of thyroid gland of various genesis (euthyroid condition, diffuse toxic goiter, hypothyreosis) was conducted with help of electron microscopy with usage of detector for registration of spectrums. Recieved data at this pathology testifies about authentic decline of oxygen and other elements in umbilical cord, placenta and uterus, what is necessary to consider at correction of uteroplacental exchange with aim to decreasing of risks of obstetric and perinatal complications.

Hypo- and hyperthyroidism have effects on brain structure and function, as well as cognitive processes, including memory. However, little is known about the influence of thyroid hormones on brain perfusion and the relationship of such perfusion changes with cognition. The present study aimed to demonstrate the effect of short-term experimental hyperthyroidism on brain perfusion in healthy volunteers and to assess whether perfusion changes, if present, are related to cognitive performance. It is known that an interaction exists between brain perfusion and cerebral oxygen consumption rate and it is considered that neural activation increases cerebral regional perfusion rate in brain areas associated with memory. Measuring cerebral blood flow may therefore represent a proxy for neural activity. Therefore, arterial spin labelling (ASL) measurements were conducted and later analysed to evaluate brain perfusion in 29 healthy men before and after ingesting thyroid hormones for 8 weeks. Psychological tests concerning memory were performed at the same time-points and the results were correlated with the imaging results. In the hyperthyroid condition, perfusion was increased in the posterior cerebellum in regions connected with cerebral networks associated with cognitive control and the visual cortex compared to the euthyroid condition. In addition, these perfusion changes were positively correlated with changes of performance in the German version of the Auditory Verbal Learning Task [AVLT, Verbaler Lern-und-Merkfähigkeits-Test (VLMT)]. Cerebellar perfusion and function therefore appears to be modulated by thyroid hormones, likely because the cerebellum hosts a high number of thyroid hormone receptors.

Background/Aim. Graves? ophthalmopthy is one of the most common causes of exophthalmos as well as the most common manifestation of Graves? disease. The treatment of Graves? ophthalmopathy includes ophthalmological and endocrinological therapy. The aim of this study was to clinically evaluate the patients with Graves? ophthalmopathy treated with corticosteroids. Methods. Evaluation of 21 patients was performed in the Ophthalmology Clinic and Endocrinology Clinic, Clinical Centre Kragujevac, in the period from 2009 to 2010. They were treated with pulse doses of intravenous corticosteroids. They were referred to ophthalmologist by endocrinologist in euthyroid condition in the active phase of Graves? ophthalmopathy (ultrasonography of orbit findings and positive findings of antithyroid stimulating hormone receptor antibody - anti-TSH R Ab). The clinical activity score (CAS) and NO SPECS classification for evaluation of disease severity were used. Ophthalmological examination includes: best corrected visual acuity, slit-lamp exam, Hertels? test, direct ophthalmoscopy and ultrasonography of the orbit. Results. According to our results 76.19% of the patients were female; mean age of the patients was 35.2 ? 5.6 years. According to CAS classification after 6 months of the treatment recovery was shown in 23.81% of the patients, partial amelioration in 47.62% and no clinical amelioration in 28.57% of the patients. We achieved better results with male, young patients with high clinical activity score. Good results were observed after the first dose of corticosteroids, much better CAS after the third dose, which maintained until 6 months after the first treatment. Conclusion. Our results signify that intravenous pulse dose of corticosteroids treatment of the patients with Graves? ophthalmopthy is safe, comfortable, clinically justified and accessible for the clinicians and patients. Positive results are achieved after the first dose with increasing trend up to the third dose, which was maintained for the next three months.

A 35-year-old male patient was admitted with fatigue and muscle weakness. He had been on methimazole due to thyrotoxicosis for 2 weeks. Laboratory tests showed overt hyperthyroidism and hypokalemia. Potassium replacement was started with an initial diagnosis of thyrotoxic hypokalemic periodic paralysis. Later on, despite the euthyroid condition and potassium chloride treatment, hypokalemia persisted. Further investigations revealed hyperreninemic hyperaldosteronism. The patient was considered to have Gitelman's syndrome (GS) and all genetic analysis was done. A c. 1145C>T, p. Thr382Met homozygote missense mutation located on solute carrier family 12, member gene 3, exon 9 was detected and GS was confirmed.

Time of the transformation to the euthyroid condition after radioiodine therapy of Grave’s disease is individual and deviates from weeks to months, what requires frequent hormones control. The aim of this study was the assessment of possibility to use HRV parameters in dynamic control after the radioiodine therapy. 77 patients were examined with 114 fT4 measurement and HRV parameters recording (before radioiodine administration and in 1, 3, 6, 12 months after). From HRV parameters two were chosen as characterizing the closest correlation with fT4 and relatively independent from each other. The whole sample was divided into the teaching set (86 measurements) and the test set (28 measurements). The decision rule was found by support vector machine in the teaching set asf(HR,SDNN) = 0.995 lg(HR) – 0.104 lg(SDNN) – 1.703, where f is the indicator of the thyroid gland function, HR – heart rate during 5-minute ECG recording; SDNN – standard deviation of RR intervals; 0.995 , 0.104 and 1.703 – correcting coefficients. If f > 0, the thyrotoxicosis takes place in a patient. If f < 0 – there is no thyrotoxicosis. The analysis of diagnostic method precision in testing set gave the following results: diagnostic sensitivity was 71%, the diagnostic specificity 79%. This method can predict thyrotoxicosis elimination or relapse with high possibility. Its use can optimize thyroid function control and refuse from fixed time hormone measurement.

There was investigation carried out in group of 54 children (42 females and 12 males) aged between 10.3 and 17.2 years (median - 13. years) for the purpose of the estimation of the clinical significance determination of the general autoantibodies to the TSH recepetor (TBII) in differential diagnostics hyperthyroidism. In 45 from 54 cases (83.3 %) there was Graves’ disease (GD) diagnosis set, while high level of TBII was detected amongst 44 from those children (97.8%). Amongst patients with subacute thyroiditis and uninodal toxic goiter together with 7 children, initially estimated by us as “AIT, hyperthyroidism” the values TBII were in limit of reference interval. But for all of that unexpectedly there was detected normal level of Ab-TPO amongst all patients in this group, and - normal echogenic in 6 from 7 cases. From the one hand, high level of Ab-TG and heterogeneous structure may be estimated as particular qualities of hyperthyroidism clinical course during AIT by amongst children. However, absence of the row of diagnostic signs with long-lasting euthyroid condition do not allow us to estimate that cases as hyperthyroidism phase of AIT. From the other hand, we can suppose that we observe the diagnostic of natural clinical course of GD cases in phase of immunological remission. The detection of normal level of TBII in absence of typical clinical signs of GD amongst children with manifestation of hyperthyroidism let us retreat from active therapeutic intervention and choose the method of dynamic observation.

A relação tireóide-gônadas sobre o perfil hematológico foi investigada em ratas Wistar adultas castradas e não castradas mantidas em hipotireoidismo induzido pela administração diária de propiltiouracil por 120 dias. Dois grupos eutireóideos não castrado e castrado foram mantidos nas mesmas condições e serviram como controle. Foram colhidos o plasma para dosagem de T4 livre e o sangue para análise hematológica. Os valores de T4 livre significativamente menores nas ratas tratadas confirmaram seu estado hipotireóideo. O hipotireoidismo causou anemia apenas em ratas com gônadas funcionais, já que a castração reverteu os efeitos do déficit de tiroxina sobre o eritrograma. Tanto o hipotireoidismo quanto o hipogonadismo apresentaram pouco significado sobre o leucograma.

Aim Thyroid dysfunctions can increase the risk of myocardial ischemia and infarction. However, the repercussions on cardiac ischemia/reperfusion (IR) injury remain unclear so far. We report here the effects of hypothyroidism and thyrotoxicosis in the susceptibility to IR injury in isolated rat hearts compared to euthyroid condition and the potential role of antioxidant enzymes. Methods Hypothyroidism and thyrotoxicosis were induced by administration of methimazole (MMZ, 300 mg/L) and thyroxine (T4, 12 mg/L), respectively in drinking water for 35 days. Isolated hearts were submitted to IR and evaluated for mechanical dysfunctions and infarct size. Superoxide dismutase types 1 and 2 (SOD1 and SOD2), glutathione peroxidase types 1 and 3 (GPX 1 and GPX3) and catalase mRNA levels were assessed by quantitative RT-PCR to investigate the potential role of antioxidant enzymes. Results Thyrotoxicosis elicited cardiac hypertrophy and increased baseline mechanical performance, including increased left ventricle (LV) systolic pressure, LV developed pressure and derivatives of pressure (dP/dt), whereas in hypothyroid hearts exhibited decreased dP/dt. Post-ischemic recovery of LV end-diastolic pressure (LVEDP), LVDP and dP/dt was impaired in thyrotoxic rat hearts, whereas hypothyroid hearts exhibited improved LVEDP and decreased infarct size. Catalase expression was decreased by thyrotoxicosis. Conclusion Thyrotoxicosis was correlated, at least in part, to cardiac remodeling and increased susceptibility to IR injury possibly due to down-regulation of antioxidant enzymes, whereas hypothyroid hearts were less vulnerable to IR injury.

To determine whether Graves' disease or primary hypothyroidism influence platelet function, we evaluated platelet aggregation in the platelet-rich plasma (PRP) from such patients. Platelet aggregation induced by adenosine diphosphate (ADP) in blood obtained from patients with untreated Graves' disease was significantly lower than normal, whereas that in patients with untreated primary hypothyroidism was relatively increased. The magnitude of platelet aggregation induced by collagen in both groups of patients resembled that induced by ADP. However, significant differences were evident between the two diseases (P < .05). In addition, we observed a significant inverse correlation between the extent of platelet aggregation and plasma levels of thyroid hormones (triiodothyronine [T3], thyroxine [T4], and free T3). Platelet aggregation returned to normal when the euthyroid condition was obtained in the patients following administration of antithyroid drugs or thyroid hormone. The findings are consistent with the possibility that thyroid hormones influence platelet aggregation partly via inhibition of myosin light-chain kinase (MLCK).

Eighty patients with multinodular colloidal euthyroid goiter were examined. Thyrotropin-releasing hormone (TRH) test was carried out in 22 patients and 7 healthy women. The results of the test indicate a clear-cut tendency to reduction of hypophyseal TTH reserve in patients with multinodular euthyroid goiter with enlarged thyroid. In other words, clinical diagnosis of an euthyroid condition in the examinees appears to be groundless, particularly in patients with stage IV multinodular euthyroid goiter who may be referred to latent hyperthyrosis group on the basis of TRH test results. Three types of STH reaction were revealed by TRH test in these patients. The authors put forward a hypothesis on STH contribution as a growth factor to the pathogenesis of multinodular colloid euthyroid goiter.

A 47-year-old male was admitted to our clinic with the complaints of chest pain, limitation of cervical movements, progressive dyspnea, and painless cervical mass. The cervical mass dimensions were approximately 15 x 20 x 25 cm. Laboratory studies revealed a recurrent hyperthyroid state. After the thyroid hormones were maintained in a euthyroid condition, a coronary angiogram was made. It revealed progressive ischemic heart disease. Combined cardiac surgery and total thyroidectomy were performed. The postoperative course was uneventful without any of the problems associated with hyperthyroidism or hypothyroidism. Combined thyroid and cardiac surgery is feasible with little risk for both operations if the perioperative levels of the thyroid hormone are maintained in a euthyroid or hypothyroid state.

Hypothyroidism decreases liver weight and delays the compensatory liver growth after partial hepatectomy (PH) as compared with the euthyroid condition. The aim of this study was to investigate, in hypothyroid rats, the mRNA expression of genes modulating these effects, focusing on c-fos and c-myc, hallmarks of hepatocyte 'priming', and on transforming growth factor-beta1 (TGF-beta1) and its receptor, the transforming growth factor-beta1 receptor-type II (TbetaR-II), negative regulators of liver growth. Euthyroid and hypothyroid male Wistar rats underwent 70% PH and total RNA was isolated from frozen liver samples removed at basal state and during regeneration, 0-144 h after surgery. In this study, we show for the first time that, in the basal liver state, hypothyroidism increased TGF-beta1 and TbetaR-II mRNA levels by 45% and 30%, respectively, as compared with the euthyroid condition and, after PH, resulted in a approximately 12-h delay in the activation of c-fos and c-myc mRNA expression. Moreover, the increase in TGF-beta1 mRNA levels, detected 24-48 h after PH in euthyroid rats, was delayed by 72 h in hypothyroid rats, occurring when a concomitant reduction in TbetaR-II was measured. These results suggest that, in hypothyroid rats, at the basal liver level, the increase in mRNA expression of genes that negatively regulate liver growth might be involved in the decrease in liver weight and that, after PH, the delay of hepatocyte 'priming' and coordinated changes in mRNA expression of negative regulators of liver regeneration might be involved in delaying the regenerative process.

Background As a consequence of the increasing application of ultrasound (US) technology, the detection of asymptomatic nonpalpable thyroid nodules has generally increased. The aim of our study was to assess if the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules (A/T) > or = 1 could be a sonographic criterion for recommending fine-needle aspiration cytology (FNAC). Methods From January 2002 to January 2004, 828 consecutive solid nonpalpable thyroid nodules were evaluated by ultrasonography, colour-Doppler and FNAC in our department. Cases were selected from 2217 patients, referred to our thyroid unit for US-guided FNAC from the greater Brescia area, an endemic zone for goitre. Entry criteria included the presence at US of a solid thyroid nodule that was nonpalpable at physical examination, euthyroid condition and no previous diagnosis of thyroid malignancy. All patients with suspicious or malignant cytology underwent surgery. Results One hundred and twenty-seven nodules with inadequate cytology were excluded from the study. Thyroid malignancy was observed in 67 (9.6%) nodules. At US, cancers presented a solid hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, intranodular vascular pattern in 56.7% and A/T > or = 1 in 83.6%. A hypoechoic appearance (OR 4.3), blurred margins (OR 2.6), microcalcification (OR 6.1), intranodular vascular pattern (OR 10.2) and A/T > or = 1 (OR 22.4) were independent risk factors of malignancy. Conclusions A/T > or = 1 in conjunction with at least one other sonographic risk factor is able to detect the majority of carcinoma and, moreover, it limits the FNAC procedures to only 15.9% of all the nodules.

Thyroid dysfunction is a well-known contributor to psychiatric morbidity. To investigate the mechanism(s) by which thyroid hormone availability affects cerebral activity, a group of thyroidectomized individuals were studied at two points in time: when markedly hypothyroid in preparation for a thyroid cancer metastatic survey and when clinically and/or biochemically euthyroid. The analysis consisted of single photon emission computed tomography (SPECT) using a lipophilic radiopharmaceutical, technetium-99m (Tc-99m) ethyl cysteinate dimer (ECD), and measurement of mood, anxiety, and psychomotor function, at both points in time. Both increases and decreases in regional cerebral radiotracer activity were found in the hypothyroid condition relative to the euthyroid condition, and the neuropsychological assessment demonstrated significantly greater depression, anxiety, and psychomotor slowing during the hypothyroid state. Increased radiotracer activity was seen in frontal and temporal regions, posterior cingulate gyrus, thalamus, and putamen. Decreased activity was seen in the occipital cortex, and the pre- and postcentral gyri. This distribution pattern is partially consistent with findings in persons with depression and anxiety unrelated to thyroid disease, supporting the link between the symptoms observed in our subjects and their marked hypothyroidism. Finally, these results support the need to consider the effect of the thyroid state on cellular mechanisms of uptake and retention of cerebral blood flow radiopharmaceuticals when studying ‘noneuthyroid’ individuals.

BACKGROUND In hyperthyroidism-complicated pregnancies, medical therapy is necessary to reach an euthyroid condition, and propylthiouracil (PTU) or methimazole (MMI) are used. These drugs are equally effective, but may cause fetal and neonatal hypothyroidism because they freely cross the placenta. Although PTU has not been significantly associated with embryo-fetal anomalies, it has been suggested that MMI might be responsible for a specific embryopathy. CASE(S) Two cases of major congenital anomalies after MMI exposure during pregnancy are reported. CONCLUSIONS PTU should be the drug of choice, and the use of MMI should be restricted to cases with allergic reactions, intolerance, or poor response to PTU. Birth Defects Research (Part A), 2003. © 2003 Wiley-Liss, Inc.

A 16-year-old Brazilian girl presented with severe growth retardation (-6.3 SDS), obesity, delayed pubertal development, facial dysmorphia, dry skin, and borderline low intelligence (IQ 89). Endocrinological evaluation showed primary hypothyroidism (no uptake of iodine-131 of the right thyroid lobe). Basal and stimulated gonadotropins were increased and ultrasonography revealed hypoplastic ovaries. The karyotype of peripheral lymphocytes was 46, X, i(Xq). The GH response in euthyroid condition after stimulation with GHRH and insulin was diminished. MRI of the pituitary region showed a suprasellar mass (12 × 15 mm) which was removed by transsphenoidal surgery because of extension to the optic chiasm. Histological examinations revealed regular pituitary tissue with hyperplasia of TSH- and FSH-producing cells. Thyroxine treatment was adjusted and GH was given. We conclude that the suprasellar mass was the consequence of long-lasting hypothalamic over-stimulation with TRH and LHRH, due to gonadal and thyroid insufficiency.

Introduction. Graves disease (GD) managements are varying. More then 40% GD patients undergo surgery in Russia. Materials and Methods. In the Centre 2920 GD patients were operated on. They made 11.7% of 24934 Thyroid (T) surgical cases during 1974-2009. This study includes 357 males (M) and 2527 females (F) observed 2-30 years after Dunhill-Drachinskaya operations (leaving 2-4 g. of some T upper pole) or thyroidectomy. Long-term results of treatment have been evaluated 2-30 years later in 336 (94.1%) males and 119 (99%) females. Statistic analysis of the data was performed using “Statistica” software. Results. Average age made 46.2 ± 2.5 years. M (43.2 ± 1.5) were significantly (p

Hyporesponsiveness of GH to insulin-induced hypoglycemia has previously been reported in hyperthyroid patients. In order to clarify the GH secretion in thyrotoxic patients, sleep-related increases in the serum GH concentration were investigated. Eight thyrotoxic females ranging in age from 7 to 15 were treated with PTU. Blood samples for measurement of GH were drawn every 15 minutes during the first few hours of sleep before and during the treatment lasting about three months. The mean maximum serum GH level before the treatment was 10.0 +/- 5.5 ng/ml (mean +/- SD); this rose to 23.2 +/- 14.6 ng/ml (P less than 0.02) during the treatment. The maximum value of more than 10 ng/ml was detected in only 3 out of the 8 patients before treatment. On the other hand, serum GH levels during PTU administration rose to above 10 ng/ml in all patients except one. It was revealed that sleep-related elevations of GH occurred early in sleep and in close association with a slow-wave EEG pattern. The results show that sleep-related GH release is low in the hyperthyroid state, but becomes significantly elevated during PTU administration. However, even in the hyperthyroid state, the sleep-related secretion of GH is closely correlated with the slow-wave sleep stage as in the euthyroid condition.

It is well known that serum TSH levels are elevated in most patients with chronic thyroiditis, even if the patient exhibits normal thyroid function tests. The determination of serum TSH levels in these patients is thought to be the most sensitive indicator of subclinical hypothyroidism. In this study, the hypophyseo-thyroid functions of untreated euthyroid patients with chronic thyroiditis were evaluated. Serum T3 levels in most of these patients were raised or at high normal levels, although serum T4 levels were in the low normal range. Serum T4 levels in patients with raised basal TSH were distributed in the low normal range. Hence, it is suggested that the decreased serum T4 stimulates TSH secretion which in turn stimulates T3 (and T4) secretion from the thyroid and the elevated T3 maintains the patient's euthyroid condition. Basal TSH levels in these patients varied from 2.5 to 37.0 muU/ml and mean +/-SD was 12.9+/-9.6 muU/ml. Thirteen out of 30 patients (43%) with normal free T4 indices showed elevated basal TSH levels. TSH responses to TRH injection were exaggerated in all euthyroid patients with raised basal TSH levels, as well as in 11 out 14 patients (78.6%) with normal basal TSH levels as well. But the maximum TSH responses after TRH injection were well correlated with basal TSH levels (gamma=0.79). The percent increases of serum T3 after TRH injection in those patients were less than those of the normal person, and there was no difference in T3 response between the normal TSH group and the group with raised TSH. Eight patients who suffered from collagen diseases (SLE:6, RA:1, PSS:1) without any evidence of thyroid disease also exhibited exaggerated TSH responses to TRH. In five out of these eight patients (62.5%) antithyroglobulin antibody was positive. This may indicate the presence of the so-called asymptomatic autoimmune thyroiditis in these patients. It is suggested that the elevated basal TSH levels in euthyroid patients with chronic thyroiditis are a much more sensitive indicator of thyroid failure than any other routine thyroid function tests. Moreover, the exaggerated TSH responses to TRH in patients with normal basal TSH levels indicated that the TRH-test is more useful for the detection of minimal thyroid failure, especially in patients having such conditions as asymptomatic automimune thyroiditis.

Three different cases of cerebral embolism occurring in combination with hyperthyroidism are reported. Case 1; a healthy 37-year-old woman presented with sudden onset of left hemiparesis and left sided hypoesthesia of all modalities. Embolism in area of the right middle cerebral artery was confirmed by angiography and CT scan. Laboratory examination revealed hyperthyroidism and anemia. Antithyroid treatment brought about euthyroid function while slight hemiparesis remained present. Case 2; a 79-year-old woman who suffered from hypertension for one year had sudden onset of disorientation and left hemiparesis. Electrocardiogram showed atrial fibrillation. The CT scan indicated infarction in the right anterior and middle cerebral artery. The patient was diagnosed as having masked hyperthyroidism. Although antithyroid medication reduced it to euthyroid condition, the patient is now bedridden with hemiparesis. Case 3; a 45-year-old man who had partial thyroidectomy for Basedow's disease and had been treated with antithyroid and antiarrhythmic therapy for 10 years. Suddenly, he was in coma with dilated right pupil and left hemiplegia. Atrial fibrillation and hypothyroid function were observed. CT scan indicated hemorrhagic infarction in the territory of the middle cerebral artery with transtentorial herniation. He died on the 59th day of hospitalization following an episode of bronchopneumonia. On the basis of the cases presented here as well as on the basis of those described in the literature it appears that thyrotoxic patients with atrial fibrillation exhibit high incidence of cerebral embolism, and prophylactic anticoagulant therapy may be recommended.

Thyroxine (T4), which is predominantly a prohormone, is produced by the thyroid gland. The biological activity of T4 is generated after enzymatic conversion of T4 into 3,3′,5-triiodothyronine (T3). In the euthyroid condition only about 20% of the total production of T3 is accomplished by the thyroid gland itself; the remainder is mainly produced by the liver from T4. Once formed, T3 is transported via the circulation to various tissues for biological action. T3 has at least two receptor sites: (1) a site of action in the nucleus with a resultant effect on gene expression, and (2) a direct effect on membrane processes, leading to an enhanced transport of amino acids and sugars. A receptor site on mitochondria has been claimed to exist, but sufficient evidence for this is lacking so far. It should be emphasized that several tissues do not only depend on circulating T3 for biological action, but also to a varying extent on T3 locally derived from T4. These differences in various tissues can be explained among other things by the presence of different types of deiodinating enzymes (for a review, see Leonard and Visser, 1986).