Dysthyroid States Research Articles

Hypothyroidism Related Kidney Disease - A Report of Two Cases

Dysthyroid state affects kidneys in multiple ways. Hypothyroidism has been described as a cause of renal dysfunction in case reports, and a few large-scale epidemiological studies have shown association of hypothyroidism with abnormalities of renal function parameters. Restoration and improvement in renal functions have also been reported with treatment of hypothyroidism. We highlight two cases where hypothyroidism contributed to renal dysfunction and the treatment of hypothyroidism led to improvement in renal function.

AN ACTIVE, SIGHT-THREATENING GRAVES’ ORBITOPATHY: A CHALLENGING CASE REPORT

Introduction: Graves’ Orbitopathy is a self-limiting autoimmune process associated with dysthyroid states, and if left untreated can lead to a number of complications, ranging from mild to sight-threatening. Corneal ulcer is one of the sight-threatening complications of Graves’ Orbitopathy. Case Report: A 22-year-old woman came with a complaint of blurred vision and retrobulbar pain on both eyes that happened gradually for 2 months, preceded by protrusion on both eyes. She had history of untreated hyperthyroid disease for 7 years. Her visual acuity was 1/60 and hand movement on the right and left eye, respectively. Anterior segment examination on both eyes revealed eyelids redness and swelling, redness and chemosis of conjunctiva, and corneal ulcer with descemetocele on her right eye. All of these clinical findings support the diagnosis of an active, sight-threatening Graves’ Orbitopathy. Discussion: The management of this patient involves; 1) thyroid function control due to the high level of thyroid function, 2) active, sight-threatening Graves’ orbitopathy management using high doses of intravenous methylprednisolon as guided by the 2016 European Group on Graves’ Orbitopathy (EUGOGO) guidelines protocol, 3) Application of amniotic membrane transplant to prevent the prolapse of intraocular tissue. Conclusion: By following EUGOGO guideline protocol, the clinical condition of this patient improved, but the management of an active, sight-threatening Graves’ Orbitopathy remains challenging and should be covered by multidisciplinary approach.

Systemic evaluation of patients with central serous chorioretinopathy: A case-control study.

To investigate the systemic associations of central serous chorioretinopathy (CSCR) with help of clinical and biochemical investigations. Case-control study. Eighty seven CSCR patients (case) and 82 Asian-Indian patients with primary non-traumatic rhegmatogenous retinal detachment (control) were recruited between July 2017 and December 2018 at a tertiary eye-care center in North India. The patients underwent ophthalmological examination and systemic evaluation based on history and biochemical investigations. Logistic regression was performed to identify the associations of CSCR. The age was similar between cases and controls (36.9 ± 7.8 years vs 35.7 ± 10.8 years, p = 0.38). On univariate analysis, the significant factors with higher odds of CSCR were alcohol use (odds ratio, OR: 3.4; 95% confidence interval: 1.36-8.53), sleep disturbance (OR: 5.44; 1.76-16.8), gastroesophageal reflux (OR: 9.34; 1.15-75.50), psychological disorder (OR: 5.78; 1.24-26.97), tuberculosis history (OR: 8.2; 1.0-67.10), serum albumin: globulin ratio (AGR) > 2 (OR: 10.43; 2.33-46.57), and serum hemoglobin (per unit increase; OR: 1.35; 1.14-1.61). Although the mean blood pressure was significantly higher in cases, the distribution among various hypertension categories was not significantly different. Exogenous steroid use and morning 8 am serum cortisol levels were not significantly different between the groups. On multivariable analysis, alcohol use (OR: 4.72; 1.33-16.76), sleep disturbances (OR: 5.04; 1.36-18.70), dysthyroid state (OR: 3.02; 1.04-8.74), serum AGR > 2 (OR: 14.28; 2.33-87.28), and serum hemoglobin (per unit increase; OR: 1.43; 1.13-1.81) were significant independent associations. Other than the previously described associations of CSCR like alcohol use and sleep disturbances, this study reports possible association with deranged serum protein and thyroid hormone profile. Further large-scale prospective studies need to validate these results.

An update on thyroid eye disease: Current knowledge, preferred practice patterns, and future therapies

Thyroid-associated ophthalmopathy (thyroid eye disease [TED], thyroid-associated orbitopathy, or Graves' orbitopathy) is the most common, yet a complex and poorly understood autoimmune orbital pathology. It occurs in association with systemic dysthyroid states, most commonly presenting with hyperthyroidism, but also occurs in association with hypothyroidism or euthyroidism. Despite the ongoing research, the pathogenesis and effective treatment strategies remain obscure, hence presenting a challenge for the treating ophthalmologist. The ocular presentation can vary from mild disease to severe irreversible sight-threatening complications. Ocular manifestations can follow the thyroid dysfunction, present parallel to it, or seldom precedes it. The ocular disease has its own natural course divided into an active and inactive phase. Scoring individual patients for the severity of disease has been frequently revised. The clinical examination, activity, and severity aid the ophthalmologist to decide the stage of the disease and come up with the treatment strategy for each patient. Management strategies include a multidisciplinary team effort. Recently, we have witnessed a leap to newer targeted biologic therapy that not only improves the course of the disease but also the quality of life of these patients. In this review, we present an update of the current understanding of etiopathogenesis, clinical features, and management options for this common yet challenging orbital inflammatory disease.

Abstract # 2038 Dysthyroidism: Is this one of suicide squads?

For a decade, South Korea has the highest suicide rate among OECD countries regardless of fabulous national insurances. But There’s no Thyroid Function Test (TFT) section and has been only examined by who wants it. The aim of this study is how much major psychiatric illness is related with thyroid function. HRV, SCL-90R and CGI was used as a method. 244 subjects were divided into euthyorid and dysthyroid hormone groups(DH) to know how many patients belong to dysthyroidism and incidence of co-morbidities. ANCOVA was used to check whether dysthyroid state relates with autonomic nervous system activities and SCL90R/CGI checklists. Multiple regression analysis were performed to find out TFT has a predictive power. 20.93% of psychiatric outpatients are turned out to have dysthyroidism. SCL-90R and CGI score in DH group showed significant relation and (p

A Review of the Phenomenon of Hysteresis in the Hypothalamus-Pituitary-Thyroid Axis.

The existence of a phase of prolonged suppression of TSH despite normalization of serum thyroid hormones over a variable period of time during the recovery of thyrotoxicosis has been documented in literature. Conversely, a temporary elevation of TSH despite attainment of euthyroid levels of serum thyroid hormones following extreme hypothyroidism has also been observed. This rate-independent lag time in TSH recovery is an evidence of a “persistent memory” of the history of dysthyroid states the hypothalamus–pituitary–thyroid (HPT) axis has encountered after the thyroid hormone perturbations have faded out, a phenomenon termed “hysteresis.” Notwithstanding its perplexing nature, hysteresis impacts upon the interpretation of thyroid function tests with sufficient regularity that clinicians risk misdiagnosing and implementing erroneous treatment out of ignorance of this aspect of thyrotropic biology. Mathematical modeling of this phenomenon is complicated but may allow the euthyroid set point to be predicted from thyroid function data exhibiting strong hysteresis effects. Such model predictions are potentially useful for clinical management. Although the molecular mechanisms mediating hysteresis remain elusive, epigenetics, such as histone modifications, are probably involved. However, attempts to reverse the process to hasten the resolution of the hysteretic process may not necessarily translate into improved physiology or optimal health benefits. This is not unexpected from teleological considerations, since hysteresis probably represents an adaptive endocrinological response with survival advantages evolutionarily conserved among vertebrates with a HPT system.

The Relationship between Population T4/TSH Set Point Data and T4/TSH Physiology.

Context. Population studies of the distribution of T4/TSH set points suggest a more complex inverse relationship between T4 and TSH than that suggested by physiological studies. The reasons for the similarities and differences between the curves describing these relationships are unresolved. Methods. We subjected the curve, derived from empiric data, describing the TSH suppression response to T4, and the more mathematically derived curve describing the T4 response to TSH, to the different possible models of population variation. The implied consequences of these in terms of generating a population distribution of T4/TSH equilibrium points (a “population curve”) were generated and compared to the empiric population curve. The physiological responses to primary hypothyroidism and hyperthyroidism were incorporated into the analysis. Conclusions. Though the population curve shows a similarly inverse relationship, it is describing a different relationship than the curve describing the suppression of TSH by T4. The population curve is consistent with the physiological studies of the TSH response to T4 and implies a greater interindividual variation in the positive thyroid T4 response to TSH than in the central inhibitory TSH response to T4. The population curve in the dysthyroid states is consistent with known physiological responses to these states.

Cardiovascular disease and thyroid function.

Thyroid function has a profound effect on the heart, and both all-cause and cardiovascular mortality rates are increased in hyperthyroidism. New-onset atrial fibrillation carries a prolonged risk for the development of hyperthyroidism, suggesting altered availability of thyroid hormones at the cellular level. Subclinical hyperthyroidism is associated with increased left ventricular mass of the heart, which reverts after obtaining euthyroidism. Mortality and risk of major cardiovascular events are increased. Subclinical hypothyroidism is also associated with subtle changes in the heart, e.g. its increased stiffness, which reverts after treatment with levothyroxine. Mortality seems mildly reduced, although the risk of myocardial infarction is increased. The risk of atrial fibrillation is related to thyroid function over the whole spectrum: from a reduced risk in overt and subclinical hypothyroidism, a progressively increased risk in people with different levels of reduced TSH to a physiologically 'dose-dependent' effect of thyroid hormones on the heart in overt hyperthyroidism. Heart failure represents an intriguing clinical situation in which triiodothyronine treatment might be beneficial. In conclusion, subclinical dysthyroid states affect the heart with subsequent changes in morbidity and mortality. Subclinical hyperthyroidism seems a more serious condition than subclinical hypothyroidism, which should affect treatment decision in a more aggressive manner.

Speech and language delay in two children: an unusual presentation of hyperthyroidism

Hyperthyroidism is rare in pre-school children. Untreated, it can have a profound effect on normal growth and development, particularly in the first 2 years of life. Although neurological manifestations of dysthyroid states are well known, specific expressive speech and language disorder as a presentation of hyperthyroidism is rarely documented. Case reports of two children with hyperthyroidism presenting with speech and language delay. We report two pre-school children with hyperthyroidism, who presented with expressive speech and language delay, and demonstrated a significant improvement in their language skills following treatment with anti-thyroid medication. Hyperthyroidism must be considered in all children presenting with speech and language difficulties, particularly expressive speech delay. Prompt recognition and early treatment are likely to improve outcome.

Thyroid associated orbitopathy

Thyroid associated orbitopathy, also known as Graves’ orbitopathy, is typically a self-limiting autoimmune process associated with dysthyroid states. The clinical presentation may vary from very mild disease to severe irreversible sight-threatening complications. Despite ongoing basic science and clinical research, the pathogenesis and highly effective therapeutic strategies remain elusive. The present article reviews the pathophysiology, clinical presentation, and management of this common, yet poorly understood disease, which remains a challenge to the ophthalmologist.

Effect of maternal thyroxine treatment on the offspring's brain development with fetal alcohol effects in the rats

Purpose:This study aimed to investigate whether exogenous thyroxine(T4) treatment to alcohol-fed dams would ameliorate the detrimental effects of alcohol on the postnatal development of neuropeptide-Y(NPY)-containing neurons of the cerebral cortex and hippocampus of the offspring. Methods:Time-pregnant rats were divided into three groups. An alcohol-fed group A received 35 calories of liquid alcohol diet daily from gestation day 6; control group B was fed a liquid diet in which dextrin replaced alcohol isocalorically; and alcohol＋T4 group C received 35 calories of liquid alcohol diet and exogenous thyroxine subcutaneously. The features of the growth and maturation of rat brain tissue were observed at 0, 7, 14, 21 and 28 postnatal days via immunohistochemistry. Results:Group C showed prominent NPY immunoreactivity in the cerebral cortex compared to group A and B at P7. In group C, NPY-containing neurons were widely distributed in the all layers of cerebral cortex after P14. Also, numerical decreases of NPY-containing neuron were not found according to increasing age in group C. A decrease of NPY-containing neurons, however, was clearly observed in group A compared to group C at P28. In the hippocampus, similar patterns appeared in groups B and C after P7. Especially, in groups B and C, NPY-containing fibers formed plexus in the cerebral cortex and hippocampus at P14. Conclusion:These results suggest that the increase of NPY synthesis caused by maternal administration of exogenous thyroxine may convalesce fetal alcohol effects, one of the effects of the dysthyroid state following maternal alcohol abuse.

Pituitary-Thyroid Axis, Thyroid Volume and Leptin in Healthy Adults

Patients with thyroid diseases usually have disturbances relating to body weight and thermogenesis. On the other hand, leptin is involved in the regulation of body weight, food intake and thermogenesis. Some studies have investigated the relationship between leptin and dysthyroid states, but the complex interactions between leptin and pituitary-thyroid axis have led to controversial results. The aims of this cross-sectional study were to investigate the relationship among basal TSH, ultrasonographic thyroid volume and leptin in a group of 268 healthy adults randomly selected from our city, L'Hospitalet de Llobregat, Barcelona, an area free of iodine deficiency. In this euthyroid group, we determined basal TSH, thyroid autoantibodies, leptin concentrations, and thyroid volume by ultrasonography, body anthropometry, and body composition. All subjects were free of goitre and were negative for anti-thyroid antibodies. Basal TSH concentrations were 1.49 +/- 0.8 mU/l in males and 1.67 +/- 0.83 mU/l in females (p = 0.6). Anti-thyroid antibodies were negative in all cases; leptin concentrations were 6.1 +/- 4 ng/ml in males and 16.8 +/- 11.7 ng/ml in females (p = 0.0001). Thyroid volume was 9.8 +/- 4.6 ml in males and 6.5 +/- 2 ml in females (p = 0.001). There were significant correlations among leptin concentrations and anthropometric and body composition variables in both sexes, without correlation with TSH concentrations. There was no significant correlation between anthropometric and body composition variables and thyroid volume in males but there was a correlation in females. In females, there was a positive correlation between leptin and thyroid volume (r = 0.181, p = 0.038). In males, there was a negative correlation between TSH concentrations and thyroid volume (r = - 0.271, p = 0.002). We did not find any correlation between leptin levels and pituitary-thyroid axis in this control population. The correlation between leptin and thyroid volume in females is probably a consequence that leptin and thyroid volume are regulated in parallel by variables relating to anthropometry and body composition.

Thyroid status affects the rat cardiac beta-adrenoceptor system transiently and time-dependently.

1. The aim of this study was to investigate the time-dependency of the influence of dysthyroid states on the beta-adrenoceptor system in rat heart left ventricle. Therefore, the influence of acute and chronic hyper- and hypothyroidism on beta-adrenoceptor-induced left ventricular responses, beta-adrenoceptor density, cardiac noradrenaline tissue concentrations, Gs alpha-proteins, and basal and stimulated adenylate cyclase activities was determined. 2. Hyperthyroid rats were obtained by feeding with thyroxine (T4)-containing rat-chow for 1, 4 and 8 weeks. Hypothyroidism was induced by adding 0.05% propylthiouracil (PTU) to the drinking water. Rats of varying ages were used in order to compensate for the differences in the duration of the treatments. Rats were aged 3 and 5 months at the end of the experiments. 3. Thyroxine treatment for 4 and 8 weeks increased the cardiac sensitivity to isoprenaline, but maximal induced inotropic responses were decreased. Cardiac ventricular beta-adrenoceptor density was increased only in rats treated with T4 for 1 week. This transient effect of hyperthyroidism on cardiac beta-adrenoceptor density was not observed in older rats. The PTU treatment resulted in a stable decrease of cardiac beta-adrenoceptor density. 4. Left ventricular tissue noradrenaline concentrations were unaffected by hyperthyroidism, where a decrease was observed in hypothyroid rats. Density of Gs alpha proteins was increased in hearts from chronic hyperthyroid rats. 5. These results indicate that the increased sensitivity to beta-adrenoceptor-mediated stimulation in chronic hyperthyroidism cannot be attributed to changes in cardiac beta-adrenoceptor density, but is probably caused by an enhanced content of Gs alpha. Accordingly, in hyperthyroidism, the beta-adrenoceptor system is influenced time-dependently, whereas hypothyroidism affects the beta-adrenoceptor system independent of time.

Thyroid hormone modulates inotropic responses, alpha-adrenoceptor density and catecholamine concentrations in the rat heart.

We investigated the influence of hyper- and hypothyroidism on basal parameters of isolated perfused hearts of rats. In addition the effects of different extracellular calcium concentrations ([Ca2+]o), the calcium entry promoter Bay K8644 and the alpha 1-adrenoceptor agonist methoxamine were investigated. Since alterations in alpha-adrenoceptor density could explain the increased sensitivity to methoxamine in hearts from hypothyroid rats, alpha 1-adrenoceptor density in the left ventricle was also established. Different time-schedules of exposure to hyper- and hypothyroidism were used to investigate whether the influence of chronic dysthyroid states on alpha 1-adrenoceptor density is transient and time-dependent. Simultaneously myocardial noradrenaline and adrenaline tissue concentrations were determined, since they might correlate with the observed changes. Hyperthyroidism was induced by feeding rats for 1, 4 and 8 weeks with 5 mg/kg L-thyroxine (T4)-containing rat chow. Hypothyroid rats were obtained by adding 0.05% propylthiouracil (PTU) to the drinking water during 1, 4 and 8 weeks. For the functional experiments animals were treated during 4 weeks, to mimic the clinical situation of a chronic endocrine disease. Langendorff hearts from hyperthyroid hearts showed an increased maximally developed relaxation velocity, whereas Langendorff hearts from hypothyroid rats showed an increased left ventricular pressure (LVP). We observed an increased maximal inotropic response to [Ca2+]o in hearts from both hyperthyroid and hypothyroid rats, indicating that both dysthyroid states interfere with the handling of calcium ions by the contractile apparatus. Unchanged responses to Bay K8644 in hearts from hyperthyroid and depressed responses in hearts from hypothyroid rats suggest that the involvement of L-type calcium channels is rather unlikely. Furthermore, the reflex increase in coronary flow in response to enhanced contractile force appeared to fail in hearts from hypothyroid rats. Sensitivity of the response to methoxamine was increased in hearts from hypothyroid rats, which was accompanied by a decrease in the number of myocardial alpha 1-adrenoceptors. Both T4 and PTU treatment resulted in a non-transient decrease of alpha 1-adrenoceptor density in left ventricular tissue. Furthermore, hypothyroidism increased the percentage of alpha 1A-binding sites, whereas in hyperthyroidism the distribution of the alpha 1-adrenoceptor subtypes was not affected. Myocardial tissue concentrations of noradrenaline and adrenaline were unchanged in hyperthyroid rats and decreased in hypothyroid rats. The present study indicates that thyroid hormones have a direct rather than a sympathetically mediated effect on alpha 1-adrenoceptor mediated myocardial functions.

Perinatal alterations of thyroid hormones and behaviour in adult rats

Several studies have shown the relevance of the neuroendocrinological system in the development and function of the nervous system. In order to observe the influence of thyroid hormones during development on the behaviour of adult rats we induced dysthyroid states during the perinatal period. Results indicate that some behaviours are more susceptible to the action of thyrpid hormones than others. We observed that the thyroid hormone deficiency causes an increase of activity in animals in spite of a large period of rehabilitation. Thyroxine-treated rats showed an anxiogenic behavioural pattern in the elevated plus-maze, while animals rehabilitated from perinatal deficit of thyroid hormones showed an anxiolitic pattern. These findings suggest that an excess of thyroid hormones has less effect on behaviour than a deficiency of these hormones.

Effect of hypo‐ and hyperthyroidism on binding of [3H]‐nitrendipine to myocardial and brain membranes.

The density of calcium channel binding sites as determined by [3H]-nitrendipine binding was found to be decreased in hearts of hyperthyroid rats but hardly altered by hypothyroidism. In contrast, dihydropyridine binding sites in the cerebral cortex were unaffected by dysthyroid states. Myocardial [3H]-nitrendipine binding sites were also decreased after treatment of the animals with isoprenaline but not in spontaneously hypertensive rats. These findings suggest that myocardial hypertrophy is not necessarily accompanied by a loss of calcium channels and that thyroid hormone regulates the density of [3H]-nitrendipine binding sites in a tissue-specific manner.

Effects of thyroid hormones on skeletal muscle bioenergetics. In vivo phosphorus-31 magnetic resonance spectroscopy study of humans and rats.

The pathophysiology of the myopathy in dysthyroid states is poorly understood. We therefore tested the effects of thyroid hormones on muscle bioenergetics in humans and rats, using in vivo 31P NMR. Two hypothyroid patients had: low phosphocreatine to inorganic phosphate ratio (PCr/Pi) at rest, increased PCr depletion during exercise and delayed postexercise recovery of PCr/Pi. Eight thyroidectomized rats did not show abnormalities at rest, but muscle work induced by nerve stimulation resulted in a significantly (P less than 0.0001) lower PCr/Pi (35-45% of control) at each of the three stimulation frequencies tested (0.25, 0.5, and 1.0 Hz). Recovery rate was markedly slowed to one-third of normal values. Thyroxine therapy reversed these abnormalities in both human and rat muscle. Five patients and six rats with hyperthyroidism did not differ from normal controls during rest and exercise but had an unusually rapid recovery after exercise. The bioenergetic abnormalities in hypothyroid muscle suggest the existence of a hormone-dependent, reversible mitochondrial impairment in this disorder. The exercise intolerance and fatigue experienced in hypothyroid muscle may be due to such a bioenergetic impairment. The changes in energy metabolism in hyperthyroid muscle probably do not cause the muscular disease in this disorder.

83. THYROXIN (T4) AFFECTS THE INTESTINAL TRANSPORT OF ELECTROLYTES

Altered states of thyroidism are associated to alterations in stool patterns. The aim of our study was to see whether T4 has a role in intestinal handling of electrolyte and water transport. In the first set of experiments, adult rats were divided into 3 groups (G-1, 2, 3) and either untreated (G-1), treated with Tapazole+ T4 (G-2) or with Tapazole alone (G-3) for 4 wks. Transepithelial bidirectional fluxes of Na and Cl were measured (and JRnet calculated) across ileal mucosa mounted in Ussing chambers. Serum T4 in G-1 (5.0±1.3μg/dl; mean±SD) and G-2 (5.2±2.2) did not differ but both differed from G-3 (2.7±0.5; p<0.001). Net ileal Cl flux (absorption “+”; secretion “-”) did not differ between G-1 (-1.2±2.4 μEq/cm2hr) and G-2 (-.2±1;6) but both differed from G-3 (+3.1±1.3; p<0.001). T4 correlated with Cl net transport (r=.61;p<0.025), and the latter with JRnet (assumed to be HCO3 net flux) (r=.65;p<0.005). In the 2nd set of experiments, rats were given orally T4 for 4 wks. They were then divided in 3 groups, according to serum T4 levels: G-4, T4 ranging 6.0-7.5 μg/dl (controls), G-5, T4 7.6-9.5 and G-6, T4 >9.6. G-5 rats showed, when compared to G-4, marked shift toward secretion in JClnet (G-5: Cl= -4.5±1.2 vs G-4: Cl= +2.36±.92, p<0.01. Again, serum T4 correlated (r= -.52, p<0.05) with Cl net transport. On the contrary, G-6 rats differed from G-5 in that they paradoxically showed higher rates of absorption for both Na and Cl. He conclude that serum T4 affects intestinal net transport of Cl by shifting it toward secretion, while it affects in the opposite manner the net transport of JR. These effects, no longer seen at the highest T4 serum levels, are consistent with a direct effect of T4 on the C1/HCO3 exchange mechanism, and may explain the alterations in stool patterns seen in dysthyroid states.

Effects of thyroid status on presynaptic alpha 2-adrenoceptor function and beta-adrenoceptor binding in the rat brain.

The effect of thyroid status on noradrenergic synaptic function in the mature rat brain was examined by measuring presynaptic alpha 2- and post-synaptic beta-adrenoceptors. Repeated triiodothyronine (T3) administration to rats (100 micrograms/kg X 14 days: hyperthyroid) caused an 18% increase in striatal beta-adrenoceptors as shown by [3H]-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU X 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic beta-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic alpha 2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic alpha 2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic alpha 2-adrenoceptor function. These results show firstly that changes in thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and post-synaptic adrenoceptor function. Secondly, there appear to be T3-induced changes in beta-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.

CHANGES IN HISTOCHEMICAL PROFILE OF RAT RESPIRATORY MUSCLES IN HYPO‐AND HYPERTHYROIDISM

Rat respiratory muscles underwent considerable changes in histochemical fibre type profile in response to hypo- and hyperthyroidism. Hypothyroidism increased the proportion of type 1 slow oxidative fibres in diaphragm and to a lesser extent in intercostal muscles. Hyperthyroidism resulted in a decreased proportion of type 1 fibres in both diaphragm and intercostals. These changes were broadly comparable to those reported previously in rat limb muscles. In normal rat respiratory muscles, the type 1 fibres were characterized by very high levels of beta-hydroxybutyrate dehydrogenase which was thought to contribute to the fatigue-resistance of these muscles. The type 2B fast glycolytic fibres, and to a lesser extent type 2A fast oxidative fibres, contained high levels of mitochondrial alpha-glycerophosphate dehydrogenase, an enzyme known to be specifically affected in dysthyroid states. The implications of the observed changes in fibre type profile with respect to the oxidative metabolism of rat respiratory muscles are discussed.