Thyroid function in patients with Parkinson's disease.
Johannessen A C,Boye A,Pakkenberg H
Acta neurologica Scandinavica
Many of the symptoms of Parkinson's disease are similar to those seen in patients with hypothyroidism. The diagnosis of myxoedema may easily be overlooked when occurring together with Parkinson's disease. We studied 52 patients with Parkinson's disease and found normal thyroid values and TSH-levels in all patients except one, who turned out to have an incipient hypothyroidism.
Hypothalamic dysfunction in Parkinson's disease patients.
Otake K,Oiso Y,Mitsuma T,Hirooka Y,Adachi K
Acta medica Hungarica
Ten patients with idiopathic Parkinson's disease (PD) (3 men and 7 women, group A) who had received no treatment for the disease; 102 patients with PD (36 men and 66 women, group B) who had undergone treatment and 45 healthy volunteers (15 men and 30 women, control group) were subject to thyrotropin-releasing hormone (TRH) tests and levodopa tests. In group A basal plasma prolactin (PRL) levels were significantly higher than in the controls both before and during treatment. Peak plasma PRL levels during TRH tests were significantly higher before treatment, but returned to the control levels during treatment. Nadir plasma PRL levels during levodopa tests were significantly increased before and during treatment. In group B basal plasma thyroid-stimulating hormone (TSH) and PRL levels were significantly higher than in the control group. Peak plasma PRL levels during TRH tests and nadir plasma PRL levels during levodopa tests were also significantly increased. The results strongly suggest a disturbance of pituitary hormone secretion due to hypothalamic dysfunction in PD patients.
Thyroid function and autoimmunity in Parkinson's disease: a study of 101 patients.
Bonuccelli U,D'Avino C,Caraccio N,Del Guerra P,Casolaro A,Pavese N,Del Dotto P,Monzani F
Parkinsonism & related disorders
Thyroid disease is the endocrine dysfunction most frequently reported in association with idiopathic Parkinson's disease (PD). The aim of this study was to assess thyroid autoimmunity and function in PD, and to verify the effect of long term l-dopa and/or dopamine therapy on thyroid function. We studied 101 consecutive PD outpatients and seventy age- and sex-matched neurological non-PD patients as controls. They were evaluated for free thyroid hormones, TSH and thyroid autoantibodies. No significant difference in the prevalence of thyroid autoimmunity and dysfunction was found between PD patients and neurological controls (10.8% in PD patients vs 10% in neurological controls). Further, treatment with l-dopa and/or dopaminergic drugs and the stage of Parkinson's disease did not affect thyroid function. In conclusion, the prevalence of thyroid autoimmunity in PD patients appeared similar to that as described in the general population, though thyroid dysfunction was observed in over than 10% of PD patients. Indeed, neurologists should be alerted to the possible complications arising from thyroid dysfunction in Parkinson's disease, but thyroid function tests should be performed only when justified on clinical grounds.
Subclinical thyroid disease in patients with Parkinson's disease.
Tandeter H,Levy A,Gutman G,Shvartzman P
Archives of gerontology and geriatrics
The objective of this study was to determine whether hypothyroidism is more common in Parkinson patients than in a control group without Parkinson, as suggested in the past. We performed a retrospective file review of all admissions to the geriatric ward during a 1-year period. Concentrations of thyroid stimulating hormone (TSH) and thyroxine (T4) from 92 Parkinson patients were compared with those of 225 randomly selected controls from the same ward. Hypothyroidism was not found to be more common in patients with Parkinson disease as previously suggested. Incidentally, we found an unexpected increase in the prevalence of abnormal thyroid laboratory tests in this group. Statistically significant differences were found in two subgroups, (1) men with Parkinson were more likely to have abnormal thyroid laboratory tests as compared with controls; and (2) 'subclinical' hyperthyroidism was found to be more prevalent in Parkinson patients than in controls. Further research in this field is warranted in non-hospitalized patients.
[A patient with Parkinson's disease complicated by hypothyroidism who developed malignant syndrome after discontinuation of etizolam].
Kawajiri Masakazu,Ohyagi Yasumasa,Furuya Hirokazu,Araki Takehisa,Inoue Naohide,Esaki Shigemitsu,Yamada Takeshi,Kira Junichi
Rinsho shinkeigaku = Clinical neurology
A 59-year-old man, who was diagnosed as having Parkinson's disease and depression seven years ago and was on oral antiparkinsonian agents, antianxiety agents, and antidepressants, developed a high fever, disturbed consciousness, and marked muscle rigidity after discontinuation of etizolam and amitriptyline. He was admitted to a nearby hospital. Hypothyroidism had been noted two months before admission. Marked muscle rigidity and increased serum CK were observed. Since discontinuation of benzodiazepine has been known to rarely trigger a neuroleptic malignant syndrome (NMS), he was diagnosed as having NMS. After receiving dantrolene and bromocriptine, these symptoms temporarily improved but he again developed consciousness disturbance, and convulsive seizures associated with an elevated serum CK. He was transferred to our hospital. On admission, the CK level was normal at 168 IU/l, while free T4 was 0.6 ng/dl (normal range, 0.9-2.3) and TSH was 108.7 mU/ml (normal range, 0.2-4.2) in serum, indicating the presence of primary hypothyroidism. As an increase in thyroid hormone dosage improved the thyroid function to normal level, his disturbed consciousness and muscle rigidity gradually improved. Convulsive seizure and recurrence of NMS in a short interval are unusual in neuroleptic malignant syndrome. In this patient, hypothyroidism may have contributed to the development of malignant syndrome through metabolic changes of the central dopaminergic system, and discontinuation of etizolam, a kind of benzodiazepine, may have triggered NMS, since there has not been reported that discontinuation of antidepressants including amitriptyline triggers NMS.
[Hypothyroidism concealed by Parkinson's disease].
García-Moreno J M,Chacón J
Revista de neurologia
AIMS:Although it is commonly recognised that diseases of the thyroids can simulate extrapyramidal disorders, a review of the causes of Parkinsonism in the neurology literature shows that they are not usually mentioned or, if so, only very briefly. The development of hypothyroidism in a patient with Parkinson s disease can go undetected, since the course of both diseases can involve similar clinical features. Generally speaking there is always an insistence on the need to conduct a thyroidal hormone study in any patient with symptoms of Parkinson, but no emphasis is put on the need to continue to rule out dysthyroidism throughout the natural course of the disease, in spite of the fact that the concurrence of both pathological conditions can be high and that, in the same way hypothyroidism can simulate Parkinson s disease, the latter can also conceal hypothyroidism. CASE REPORT:We report the case of a female patient who had been suffering from Parkinson s disease for 17 years and started to present on off fluctuations that did not respond to therapy. Hypothyroidism was observed and the hormone replacement therapy used to resolve the problem allowed the Parkinsonian fluctuations to be controlled. CONCLUSIONS:We believe that it is very wise to suspect hypothyroidism in patients known to be suffering from Parkinson s disease, and especially so in cases where the clinical condition worsens and symptoms no longer respond properly to antiparkinsonian treatment. These observations stress the possible role played by thyroid hormones in dopaminergic metabolism and vice versa.
Parkinson's disease and thyroid dysfunction.
Munhoz Renato P,Teive Helio A G,Troiano André R,Hauck Patrícia R,Herdoiza Leiva Maria H B,Graff Hans,Werneck Lineu C
Parkinsonism & related disorders
BACKGROUND:Although no causal linkage between hypothyroidism and Parkinson's disease (PD) has been demonstrated so far, both share common manifestations and coexistence can be a source of diagnostic delay and confusion. PURPOSE:To assess thyroid function in patients with PD. SCOPE:Ninety-five PD patients and 102 age-matched controls were assessed for hypothyroidism through clinical evaluation and laboratory screening. RESULTS:In the PD group 13.7% were hypothyroid versus 10.8% in the control group. Statistical analysis did not show a significant difference (p = 0.3681). CONCLUSION:Although hypothyroidism was not more prevalent in our PD patients in comparison with the control group, we believe that given the potential overlap of symptoms and signs, thyroid function should be assessed in patients showing worsening of symptoms that cannot be explained by disease progression or resistance to therapy adjustment; screening should take into account the particular acute effect of levodopa on serum TSH levels.
Metaiodobenzylguanidine (MIBG) uptake in Parkinson's disease also decreases at thyroid.
Matsui Hideaki,Udaka Fukashi,Oda Masaya,Tamura Akiko,Kubori Tamotsu,Nishinaka Kazuto,Kameyama Masakuni
Annals of nuclear medicine
BACKGROUND:Decreased cardiac metaiodobenzylguanidine (MIBG) uptake was reported in Parkinson's disease and this contributes to the differential diagnosis between Parkinson's disease and other forms of parkinsonism such as multiple system atrophy. However, decreased MIBG uptake of the thyroid has not been demonstrated. OBJECTIVE:To compare MIBG uptake of the thyroid among Parkinson's disease, multiple system atrophy and controls. METHODS:Twenty-six patients with Parkinson's disease, 11 patients with multiple system atrophy and 14 controls were examined in this study. Planar images were taken 15 minutes (early images) and 3 hours (late images) after intravenous injection of 111 MBq 123I-MIBG. RESULTS:MIBG uptake of the thyroid on early images decreased significantly in Parkinson's disease compared to controls (p < 0.0001) and multiple system atrophy (p = 0.018). MIBG uptake of the thyroid on early images decreased significantly also in multiple system atrophy compared to controls (p = 0.027). On late images, thyroid uptake differed significantly only between Parkinson's disease and controls (p = 0.010). CONCLUSIONS:Our study is the first to demonstrate decreased MIBG uptake of the thyroid in Parkinson's disease. Sympathetic nervous denervation of Parkinson's disease occurred not only in the heart but also in the thyroid.
Hyperthyroidism exaggerating parkinsonian tremor: a clinical lesson.
Kim Hee Tae,Edwards Mark J,Lakshmi Narsimhan R,Bhatia Kailash P
Parkinsonism & related disorders
We present the clinical description of a 70-year-old man with parkinsonian tremor, which was severely exaggerated by hyperthyroidism. Clinical diagnosis of hyperthyroidism was overshadowed by the parkinsonian symptoms. Anti-thyroid treatment had a beneficial effect on the exaggerated parkinsonian tremor. This case report highlights that thyroid dysfunction should be considered in the differential diagnosis of aggravated tremor in Parkinson's disease which seems refractory to increased dosages of anti-parkinsonian drugs.
Pituitary function and the somatotrophic system in patients with idiopathic Parkinson's disease under chronic dopaminergic therapy.
Schaefer S,Vogt T,Nowak T,Kann P H,
Journal of neuroendocrinology
Idiopathic Parkinson's disease and dopaminergic medication may influence pituitary hormone secretion. The present study aimed to reveal any abnormalities of the somatotrophic system induced by the disease itself and/or the dopaminergic therapy. Investigations of other pituitary hormones under basal and stimulated conditions, as well as an analysis of body composition, were also performed. This was a controlled diagnostic study in which luteinising hormone-releasing hormone, thyroid-releasing hormone, corticotrophin-releasing hormone and arginine hydrochloride were administered to ten patients with idiopathic Parkinson's disease under dopaminergic medication. Basal and stimulated hormone concentrations and bioelectrical impedance analyses were compared with those of healthy, age-matched controls. Basal growth hormone (GH) at -30 and 0 min was higher in Parkinsonian patients (2.74 +/- 3.79 ng/ml versus 0.53 +/- 0.10 ng/ml and 2.12 +/- 2.44 ng/ml versus 0.51 +/- 0.03 ng/ml; P < 0.05). The area under the GH curve after stimulation was greater in Parkinsonian patients (502.4 +/- 202.6 ng x min/ml versus 312.0 +/- 98.5 ng x min/ml; P < 0.05), depending on higher basal GH levels, rather than a greater arginine response. No differences in insulin growth factor (IGF)-1 or IGF-BP3 concentrations were detected. There were no differences between the groups in basal and stimulated gonadotrophic, corticotrophic and thyrotrophic function, or body composition. Prolactin was below the detection limit in the patients during the course of the study. Parkinsonian patients experience marked hypoprolactinaemia and repeated stimulation of GH secretion during chronic dopaminergic therapy. Our findings suggest a peripheral GH resistance in these chronically-treated patients.
Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease.
Aziz N A,Pijl H,Frölich M,Roelfsema F,Roos R A C
Journal of neuroendocrinology
Recently, a massive loss of both hypocretin and melanin-concentrating hormone (MCH) neurones was found in the hypothalamus of Parkinson's disease (PD) patients. Because both hypocretin and MCH play a key role in the regulation of sleep, energy homeostasis and autonomic function, partly by modulation of the somatotrophic, thyrotrophic and lactotrophic axes, neuroendocrine dysregulation may contribute to some of the non-motor features of PD. In eight de novo, medication-free PD patients and eight age-, sex- and body mass index-matched controls, we measured serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH) and prolactin every 10 min for 24 h. Auto-deconvolution, cosinor and approximate entropy analysis were applied to quantify GH, TSH and prolactin secretion rates, diurnal rhythmicity, as well as regularity of hormone release. Sleep was polygraphically-recorded throughout the night. Total 24-h secretion of GH (191 ± 31 versus 130 ± 39 mU/l/24 h), TSH (38 ± 9 versus 36 ± 2 mU/l/24 h) and prolactin (102 ± 14 versus 116 ± 17 μg/l/24 h), as well as their diurnal rhythmicity and regularity of release, were not significantly different between PD patients and controls (all P ≥ 0.12). Fasting levels of insulin-like growth factor-1 were also unaltered in PD patients. However, free thyroxine (T(4) ) levels were significantly higher in PD patients compared to controls (16.19 ± 0.80 versus 13.88 ± 0.40 pmol/l; P = 0.031). In PD patients, prolactin levels were related to disease duration (r = 0.76, P = 0.028), whereas both GH (r = -0.91, P = 0.002) and free T(4) (r = -0.71, P = 0.050) levels correlated inversely with body fat content. Apart from a mild increase in free T(4) levels, we found no indications for altered somatotrophic, thyrotrophic and lactotrophic axes activity in early-stage PD patients.
Impaired hepatic function and central dopaminergic denervation in a rodent model of Parkinson's disease: a self-perpetuating crosstalk?
Vairetti Mariapia,Ferrigno Andrea,Rizzo Vittoria,Ambrosi Giulia,Bianchi Alberto,Richelmi Plinio,Blandini Fabio,Armentero Marie-Therese
Biochimica et biophysica acta
In Parkinson's disease (PD), aside from the central lesion, involvement of visceral organs has been proposed as part of the complex clinical picture of the disease. The issue is still poorly understood and relatively unexplored. In this study we used a classic rodent model of nigrostriatal degeneration, induced by the intrastriatal injection of 6-hydroxydopamine (6-OHDA), to investigate whether and how a PD-like central dopaminergic denervation may influence hepatic functions. Rats received an intrastriatal injection of 6-OHDA or saline (sham), and blood, cerebrospinal fluid, liver and brain samples were obtained for up to 8 weeks after surgery. Specimens were analyzed for changes in cytokine and thyroid hormone levels, as well as liver mitochondrial alterations. Hepatic mitochondria isolated from animals bearing extended nigrostriatal lesion displayed increased ROS production, while membrane potential (ΔΨ) and ATP production were significantly decreased. Reduced ATP production correlated with nigral neuronal loss. Thyroid hormone levels were significantly increased in serum of PD rats compared to sham animals while steady expression of selected cytokines was detected in all groups. Hepatic enzyme functions were comparable in all animals. Our study indicates for the first time that in a rodent model of PD, hepatic mitochondria dysfunctions arise as a consequence of nigrostriatal degeneration, and that thyroid hormone represents a key interface in this CNS-liver interaction. Liver plays a fundamental detoxifying function and a better understanding of PD-related hepatic mitochondrial alterations, which might further promote neurodegeneration, may represent an important step for the development of novel therapeutic strategies.
The role of Thyrotropin Releasing Hormone in aging and neurodegenerative diseases.
Daimon Caitlin M,Chirdon Patrick,Maudsley Stuart,Martin Bronwen
American journal of Alzheimer's disease (Columbia, Mo.)
Thyrotropin releasing hormone (TRH) is primarily known as the central regulator of the hypothalamic-pituitary-thyroid (HPT) axis. However, TRH also exerts a variety of central nervous system effects independent from its activity in the HPT axis. With advancing age, decreases in TRH synthesis, expression, and activity have been demonstrated. Associated with this emerging evidence suggests that TRH is implicated in neurodegenerative diseases of aging, including Alzheimer's disease and Parkinson's disease. TRH and its synthetic analogs have been recognized as trophic factors in neurons of the diencephalon and spinal cord, and as neuroprotectants against oxidative stress, glutamate toxicity, caspase-induced cell death, DNA fragmentation, and inflammation. In this review, we will provide an overview of some of the roles of TRH, outside of the HPT axis, associated with pathological aging and neurodegeneration and we shall discuss the potential of TRH and TRH analogs for the treatment of neurodegenerative diseases.
Thyroid MIBG uptake in Parkinson's disease with diabetes mellitus.
Jang Wooyoung,Kim Joong-Seok,Cho Jin Whan,Ahn Jin Young,Choi Yun Young,Kim Hee-Tae
Clinical autonomic research : official journal of the Clinical Autonomic Research Society
In our work, we investigated thyroid and cardiac MIBG uptake as potential differential markers. We observed reduced cardiac uptake of MIBG in PD and diabetic CAN, in agreement with the previous studies. However, there was a significant difference between the PD and diabetic cardiac autonomic neuropathy groups with respect to early and delayed thyroid MIBG uptake, in that reduced thyroid MIBG uptake was seen in PD but not in diabetic autonomic neuropathy. We therefore propose that this parameter could be a marker for identifying parkinsonism when it presents together with DM.
Thyroid-induced worsening of parkinsonian tremor resistant to drugs and subthalamic nucleus deep brain stimulation.
Minár Michal,Valkovič Peter
Case reports in neurological medicine
Introduction. Symptoms of both hypothyroidism and thyrotoxicosis can be easily overlooked in patients with Parkinson's disease (PD). We report on a patient whose parkinsonian tremor worsened and proved refractory not only to common treatment, but also to deep brain stimulation (DBS). Case Presentation. A 61-year-old woman with advanced PD underwent bilateral subthalamic DBS, with an excellent outcome. Twenty-one months after the surgery, however, patient's resting/postural tremor markedly worsened. There was a slight improvement for 1 month after repeated adjustments of DBS parameters, but then the tremor worsened again. Since even a minimal increase of the dose of dopaminergic drugs caused extremely severe dyskinesias, an anticholinergic drug biperiden and benzodiazepine clonazepam were introduced, what helped for another month. With the onset of severe diarrhoea, a laboratory workup was performed. Thyrotoxicosis was detected. During treatment with the antithyroid agent carbimazole, the parkinsonian tremor clearly improved within two weeks. Conclusion. A hyperthyroid state can markedly exaggerate all forms of tremor, as well as other types of movement disorders. This condition can be overlooked or masked by other symptoms. Therefore, if the tremor in a patient with PD gradually worsens and proves resistant to the usual treatment, examine the thyroid gland.
Thyroid status and cognitive function in euthyroid patients with early Parkinson's disease.
Choi Seong-Min,Kim Byeong C,Choi Kang-Ho,Nam Tai-Seung,Kim Joon-Tae,Lee Seung-Han,Park Man-Seok,Kim Myeong-Kyu,Cho Ki-Hyun
Dementia and geriatric cognitive disorders
BACKGROUND:Alterations in thyroid hormone (TH) levels may be related to the pathogenesis of mild cognitive impairment (MCI) and dementia. Cognitive deficits are common in Parkinson's disease (PD) patients. The aim of this study was to investigate whether variations within the normal ranges of thyroid function are related to cognitive function in early PD without dementia. METHODS:Eighty-four euthyroid patients with early PD underwent evaluation of their thyroid status, including measures of thyroid-stimulating hormone (TSH), total triiodothyronine (tT3) and free thyroxine (fT4), and comprehensive neuropsychological tests. RESULTS:The 46 patients of the PD-MCI group did not differ in the serum levels of TH compared to the 38 patients of the PD-normal cognition group. fT4 levels were inversely associated with the Mini-Mental State Examination (MMSE) score and neuropsychological tests of attention and visuospatial and executive function. TSH and tT3 levels were not related to cognitive performances. After controlling for demographic and clinical variables, multiple regression analyses indicated statistically significant associations between fT4 concentrations and MMSE score and neuropsychological tests of executive function. CONCLUSIONS:This study supports a relationship between the thyroid status and cognitive function in euthyroid early PD patients, with higher concentrations of fT4 being associated with a poor performance of executive function.
May the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and sporadic Parkinson's disease?
Fernández Emilio,García-Moreno José-Manuel,Martín de Pablos Angel,Chacón José
Antioxidants & redox signaling
The research group has detected nitrosative stress and a singular version of nitrosylated serum α-synuclein in serum of Parkinson's disease (PD) patients. Dysfunction of the thyroid gland has been proposed to be linked to this disease. The aim of the study was to know if the thyroid gland is involved in idiopathic PD and nitrosative stress. We studied 50 patients (early and advanced disease patients), 35 controls, and 6 subjects with thyroidectomy. Clinical characteristics, serum thyroperoxidase levels, and 3-nitrotyrosine proteins were analyzed. Enzyme-linked immunosorbent assay and immunoblotting methods were employed. The findings indicated that the prevalence of two thyroid dysfunctions (hyper- or hypothyroidism) was not found to be different in patients relative to controls. However, the levels of the enzyme thyroperoxidase were found to be elevated in early disease patients (p<0.006), not in advanced disease subjects, and these levels were negatively correlated with serum 3-nitrotyrosine proteins (p<0.05), the indicators of nitrosative stress. The thyroidectomized subjects showed very low levels of serum 3-nitrotyrosine proteins (78% reduction vs. controls) and, among these proteins, the nitrosylated serum α-synuclein was nearly absent. These observations lead to the hypothesis that the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and they could influence Parkinsonian nitrosative stress as well as nitrosylation of serum α-synuclein, a potentially pathogenic factor.
Thyroid hormone level is associated with motor symptoms in de novo Parkinson's disease.
Umehara Tadashi,Matsuno Hiromasa,Toyoda Chizuko,Oka Hisayoshi
Journal of neurology
Sympathetic denervation has been observed not only in the myocardium but also in the thyroid of patients with Parkinson's disease (PD). We investigated whether sympathetic denervation as indicated by decreased cardiac (123)I-meta-iodobenzylguanidine uptake is associated with the levels of thyroid hormones and whether the levels of thyroid hormones affect clinical manifestations in patients with PD. The subjects were 75 patients with de novo PD and 20 age-matched healthy controls. We examined the levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and evaluated the associations of these levels with cardiac (123)I-meta-iodobenzylguanidine uptake and motor symptoms. The results showed that the free triiodothyronine level was below the normal range in 29 patients (approximately 40 %) and was significantly lower in the patients with PD than in the controls. The decreased free triiodothyronine level was associated with akinetic-rigid motor subtype and washout ratio of cardiac (123)I-meta-iodobenzylguanidine scintigraphy. The free triiodothyronine level negatively correlated with disease severity. Thyroid-stimulating hormone level was within normal range. However, its level was lower in patients with tremor-dominant type or mixed type than in those with akinetic-rigid type. All correlations of these variables with the levels of thyroid hormones remained statistically significant on multiple regression analysis. Our results suggest that the thyroid hormone level, especially the free triiodothyronine level, is closely related to motor symptoms in patients with de novo PD. Further studies are needed to clarify whether the decreased hormone levels have functional roles in motor and non-motor symptoms.
What increases the risk of malnutrition in Parkinson's disease?
Tomic Svetlana,Pekic Vlasta,Popijac Zeljka,Pucic Tomislav,Petek Marta,Kuric Tihana Gilman,Misevic Sanja,Kramaric Ruzica Palic
Journal of the neurological sciences
Parkinson's disease (PD) patients are at a higher risk of malnutrition. The prevalence has been estimated to 0-24%, while 3%-60% of PD patients are reported to be at risk of malnutrition. To date, there is no clear explanation for malnutrition in these patients. The aim of this study was to determine the prevalence of malnutrition and to analyze factors that influence its appearance. The Mini Nutritional Assessment (MNA) was used to determine normal nutritional status; at risk of malnutrition; and already malnourished status. The Unified Parkinson's Disease Rating Scale (UPDRS) parts III and IV, Hoehn and Yahr scale (H&Y scale), Beck Depression Inventory (BDI), Mini Mental State Examination (MMSE), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale - eating part (QUIP-RS) and Mini Nutritional Assessment (MNA) were used to evaluate the factors affecting patient nutritional status. Out of 96 patients, 55,2% were at risk of malnutrition, while 8,3% had already been malnourished. Age, H&Y scale, UPDRS part III, 'off' periods and depression influence negatively on MNA. More patients with 'off' periods were rigor dominant. Thyroid gland hormone therapy was related to malnutrition, while patients with normal nutritional status used ropinirole more often than pramipexole. Factors affecting nutritional status are age, motor symptoms and stage severity, 'off' states, rigidity dominant type with 'off' states, and thyroid hormone replacement therapy. Ropinirole exhibited the possible 'protective' effect against malnutrition.
Hypothyroidism-induced Reversible Encephalopathy as a Cause of Aggravation of Parkinsonism and Myoclonus in Parkinson's Disease.
Ehm Gwanhee,Kim Han-Joon,Jeon Beomseok
Tremor and other hyperkinetic movements (New York, N.Y.)
Background:Myoclonus and encephalopathy are unusual in patients with Parkinson's disease (PD). Case report:We describe the case of a 59-year-old male with PD who developed myoclonus and encephalopathy. Underlying hypothyroidism was revealed after admission and treated with levothyroxine. Myoclonus and encephalopathy were completely resolved following thyroid hormone replacement. Discussion:Hypothyroidism can cause reversible myoclonus and encephalopathy along with unusual aggravation of parkinsonism symptoms in patients with PD.
The Thyroid Hormone-target Gene Rhes a Novel Crossroad for Neurological and Psychiatric Disorders: New Insights from Animal Models.
Napolitano Francesco,D'Angelo Livia,de Girolamo Paolo,Avallone Luigi,de Lange Pieter,Usiello Alessandro
Ras homolog enriched in striatum (Rhes) is predominantly expressed in the corpus striatum. Rhes mRNA is localized in virtually all dopamine D1 and D2 receptor-bearing medium-sized spiny neurons (MSNs), and cholinergic interneurons of striatum. Early studies in rodents showed that Rhes is developmentally regulated by thyroid hormone, as well as by dopamine innervation in adult rat, monkey and human brains. At cellular level, Rhes interferes with adenosine A2A- and dopamine D1 receptor-dependent cAMP/PKA pathway, upstream of the activation of the heterotrimeric G protein complex. Besides its involvement in GPCR-mediated signaling, Rhes modulates Akt pathway activation, acts as E3-ligase of mutant huntingtin, whose sumoylation accounts for neurotoxicity in Huntington's disease, and physically interacts with Beclin-1, suggesting its potential involvement in autophagy-related cellular events. In addition, this protein can also bind to and activate striatal mTORC1, one of the key players in l-DOPA-induced dyskinesia in rodent models of Parkinson's disease. Accordingly, lack of Rhes attenuated such motor disturbances in 6-OHDA-lesioned Rhes knockout mice. In support of its role in MSN-dependent functions, several studies documented that mutant animals displayed alterations in striatum-related phenotypes reminiscent of psychiatric illness in humans, including deficits in prepulse inhibition of startle reflex and, most interestingly, a striking enhancement of behavioral responses elicited by caffeine, phencyclidine or amphetamine. Overall, these data suggest that Rhes modulates molecular and biochemical events underlying striatal functioning, both in physiological and pathological conditions.
Dopamine neuron induction and the neuroprotective effects of thyroid hormone derivatives.
Lee Eun-Hye,Kim Sang-Mi,Kim Chun-Hyung,Pagire Suvarna H,Pagire Haushabhau S,Chung Hee Yong,Ahn Jin Hee,Park Chang-Hwan
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive movement disturbances caused by the selective loss of dopamine (DA) neurons in the substantia nigra. Despite the identification of the causal mechanisms underlying the pathogenesis of PD, effective treatments remain elusive. In this study, we observed that a low level of fetal bovine serum (FBS) effectively induced DA neurons in rat neural precursor cells (NPCs) by enhancing nuclear receptor-related 1 protein (NURR1) expression. Among the various components of FBS, the thyroid hormones triiodothyronine (T3) and thyroxine (T4) were identified as key factors for the induction of DA neurons. Since an overdose of thyroid hormones can cause hyperthyroidism, we synthesized several thyroid hormone derivatives that can partially activate thyroid hormone receptors and induce the complete differentiation of NPCs into DA neurons. Two derivatives (#3 and #9) showed positive effects on the induction and maturation of DA neurons without showing significant affinity for the thyroid hormone receptor. They also effectively protected and restored DA neurons from neurotoxic insults. Taken together, these observations demonstrate that thyroid hormone derivatives can strongly induce DA neuron differentiation while avoiding excessive thyroid stimulation and might therefore be useful candidates for PD treatment.
Association Between Thyroid Diseases and Parkinson's Disease: A Nested Case-Control Study Using a National Health Screening Cohort.
Kim Ji Hee,Lee Heui Seung,Ahn Jun Hyong,Oh Jae Keun,Chang In Bok,Song Joon Ho,Wee Jee Hye,Min Chan Yang,Yoo Dae Myoung,Choi Hyo Geun
Journal of Parkinson's disease
BACKGROUND:Although the dopaminergic system is interconnected with the hypothalamic-pituitary-thyroid axis, few studies have explained the causal relationship between thyroid disease and Parkinson's disease (PD). OBJECTIVE:The goal of this study was to investigate the association between thyroid diseases and PD in Korean residents. METHODS:The Korean National Health Insurance Service-National Sample Cohort, which includes individuals aged ≥40 years, was assessed from 2002 to 2015. A total of 5,586 PD patients were matched by age, sex, income, and the region of residence with 22,344 control participants at a ratio of 1:4. In the PD and control groups, previous histories of levothyroxine treatment, goiter, hypothyroidism, thyroiditis, and hyperthyroidism were investigated. RESULTS:The rates of levothyroxine treatment for more than 3 months, hypothyroidism, and hyperthyroidism were higher in the PD group than the control group (3.2%, 3.8%, and 2.8% vs. 2.5%, 2.9%, and 1.9%, respectively, p < 0.05). The adjusted odds ratios (ORs) in model 2, which was adjusted for all potential confounders, for hypothyroidism and hyperthyroidism in the PD group were 1.25 (95% confidence interval (CI) 1.01-1.55, p = 0.044) and 1.37 (95% CI 1.13-1.67, p = 0.002), respectively. In subgroup analyses, the association between hypothyroidism and PD was maintained in men older than 70 years and the association between hyperthyroidism and PD was maintained in women younger than 70 years. CONCLUSION:Both hyperthyroidism and hypothyroidism were associated with higher risk of PD, particularly for women younger than 70 years and men older than 70 years, respectively.
Shedding light on thyroid hormone disorders and Parkinson disease pathology: mechanisms and risk factors.
Mohammadi S,Dolatshahi M,Rahmani F
Journal of endocrinological investigation
Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons. Dopaminergic system is interconnected with the hypothalamic-pituitary-thyroid axis. Dopamine (DA) upregulates thyrotropin releasing hormone (TRH) while downregulating thyroid stimulating hormone (TSH) and thyroid hormones. Moreover, TRH stimulates DA release. PD is associated with impaired regulation of TSH and thyroid hormones (TH) levels, which in turn associate with severity and different subtypes of PD, while levodopa and bromocriptine treatment can interfere with hypothalamic-pituitary-thyroid axis. Thyroid disturbances, including hypothyroidism, Hashimoto's thyroiditis (HT), hyperthyroidism and Graves' disease (GD) not only increase the risk of PD but also share some clinical signs with PD. Also, several genes including RASD2, WSB1, MAPT, GIRK2, LRRK2 and gene products like neurotensin and NOX/DUOX affect the risk for both PD and thyroid disease. Hypothyroidism is associated with obesity, hypercholesterolemia, anemia and altered cerebral blood flow which are associated with PD pathology. Herein we provide a comprehensive view on the association between PD and thyroid hormones regulation and dysregulations, hoping to provide new avenues towards targeted treatment of PD. We performed a comprehensive search in literature using Pubmed and Scopus, yielding to a total number of 36 original articles that had addressed the association between thyroid hormone disorders and PD.
Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with Parkinson's disease.
Tan Yinyin,Gao Lei,Yin Qingqing,Sun Zhanfang,Man Xiao,Du Yifeng,Chen Yan
The International journal of neuroscience
This study is to investigate the relationship between thyroid function and Parkinson's disease (PD). Totally 77 PD patients were included, who were divided into tremor-dominant-type (TDT), akinetic-rigid-type (ART) and mixed-type (MXT) subgroups. Parkinsonism severity and stage was assessed by modified H-Y stage. Thyroid-stimulating hormone (TSH), fT3 and fT4 levels were detected to analyze thyroid function. Parameters of thyroid homeostasis, including thyroid's secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD) and Jostel's TSH index and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated and compared. Thyroid hormone levels in PD patients were lower than normal controls. Patients with TDT/MXT had significantly higher fT4 level than those with ART. TSH levels were 1.73 ± 0.93 and 2.06 ± 1.04 ulU/ml for patients with TDT/MXT and ART, respectively. The patients in the TDT/MXT group had significantly lower SPINA-GD while significantly higher SPINA-GT than ART group. The fT3 level was significantly higher in early group than advanced group. TSH index in the early group was significantly higher than the advanced group. The fT4 level was negatively correlated with UPDRS motor score. Univariate and multivariable logistic regression analysis indicated that fT4 was positively correlated with PD motor subtype, which disappeared after adjusting for confounding factors. The fT3 level was negatively correlated with PD disease severity, even after adjusting for confounding factors. In female PD patients, fT4 level in TDT/MXT group was significantly higher than ART group. Male PD patients had higher fT4 levels in early patients than advanced patients. Percentage of patients exhibiting ART was decreased significantly in higher fT4 level subgroups. With the increase of TSH index and TTSI, the proportion of advanced PD patients gradually decreased. The proportion of PD patients with TDT/MXT motor subtype gradually increased with the quartiles of SPINA-GT. Thyroid hormone levels and structural parameters of thyroid homeostasis are correlated with motor subtype and disease severity in euthyroid patients with PD.