NEUROLOGICAL MANIFESTATIONS IN SPORADIC EUTHYROID GOITER

INTRODUCTION

Sporadic goiter or simple euthyroid thyromegaly it is described by global, moderate volume increasing of the thyroid, without signs of hypo or hyperthyroidism or of inflammatory or neoplastic proliferation[1].

Sporadic goiter occurs in any geographic area, frequently being mistaken for endemic oligosymptomatic goiter [2].

It’s etiology is unclear, as it may occur in areas with normal iodine intake, but iodine per gram of gland and the degree of thyroglobulin iodization are diminished. There are supposed deficits in the intrathyroidal iodine metabolism [3]. TSH level is increased, which explains the thyroid hypertrophy.

It can be more frequent in some members of the family, which would imply genetic factors that reduce the resistance to aggressions capable of modifying the iodine uptake and thyroid hormone biosynthesis.

Semiologically, it presents itself under the form of a global thyroid hypertrophy, predominant in the right lobe with renitent consistency, regular surface, nonadherent to underlying structures [4]. It is not painful, it does not present adenopathies, nor histopathologic modifications. Bulky forms create aesthetic discomfort causing a phenomena of compression [5].

It occurs in young women, in stressful situations, prolonged lactation, puberty and pregnancy. There are also goiter forming substances that block the iodine intake into the thyroid, they are present in some foods, in contraceptive treatments, in fluorine, in antithyroid drugs, estrogens or in diarrhea syndrome type diseases or nephrotic syndrome [1].

Multinodular forms may occur due to evolution.

THE PURPOSE OF THE STUDY

We conducted a clinical study supported by laboratory examinations which had as purpose to determine the neurological manifestations of sporadic euthyroid goiter, referring to frequency, clinical and therapeutic response of neurological determinations in this type of thyroid pathology, and revealing the diagnostic difficulties of the damage done to the nervous system by this type of thyroid pathology.

MATERIAL AND METHOD

1. The type of the study:

The research followed the recommended methodology for conducting the clinical and epidemiological studies,

2. Choosing the subjects:

The study focused on a group of 160 patients with sporadic euthyroid goiter, who were examined in the neurology and endocrinology sections in Galati Emergency Hospital, followed for a period of five years. Patients were examined clinically and paraclinically every 3 months.

Clinical examination was associated with paraclinical tests. Paraclinical data were recorded in the observations sheets.

3. Data gathering:

For the clinical diagnosis of hyperthyroidism the Newcastle index was used, and in the clinical assessment of the hypothyroidism the Billewicz index was used. For the paraclinical endocrinological diagnosis there were used: hormone dosage T3, FT3, T4, FT4, TSH, thyroid ultrasound exam and thyroid scintigraphy with 99mTcO4, in doses of 2mCi, thyroid biopsy with a thin needle puncture, sella trucica radiography, CT brain scan or miediastinum scan, brain MRI, biochemical usual tests of blood and urine, EKG.

For the study of neurological damage there were used: electroneuromyography data, VCM, VCS, ocular fundus exam, EEG, nervous and muscular biopsy with microscopic evaluation, anatomopathological exam of some parts gathered after brain excision, lung x-ray, miediastinum x-ray, bone x-ray, Doppler ECD exam, TCD, CSF study.

4. Processing and statistical analysis of the data:

Processing and statistical data analysis were performed using specialized software SPSS version

11. We calculated central tendency indicators, structural indicators and frequency indicators.

The specific objectives of the clinical trial of patients with sporadic euthyroid goiter had as purpose:

– Detecting the main neurological manifestations;

– Evaluating the frequency in such cases;

– Changes in neurological response to the treatment for the thyroid pathology.

In the studied group we followed 160 cases of patients with euthyroid goiterwhich presented clinical thyromegaly.

The clinical trial of cases with sporadic euthyroid goiter had the following specific objectives:

– Identifying neurological damage;

– Determining the frequency of neuropsychiatric manifestations;

– Setting the stage of neurological damage;

In all the cases, the goiter was associated with normal values of thyroid hormones: T3, T4, TSH.

The gender distribution of the study group (fig. 1) was the following:

–1.25% – male (2 cases);

– 98.75% – female (158 cases);

The prevalence of sporadic euthyroid goiter in women is significantly higher (p<0.001) compared to men.

Fig. 1: Gender distribution of the cases with sporadic

Urban and rural distribution of the study group was the following:

– Rural environment – 18.75% (30 cases);

– Urban environment – 81.25% of the patients (130 cases) – fig. 2.

Fig. 2: Urban and rural distribution of the patients with sporadic goiter from the study group.

Smoking prevalence in the study group was of 13.75%, 22 patients being smokers.

Age distribution of the patients with sporadic goiter in the study group was the following (fig. 3):

– Under 20 years old – 2 cases – 1.25%;

– 20-29 years old – 24 cases – 15%;

– 30-39 years old – 26 cases – 16.25%;

– 40-49 years old – 44 cases – 27.5%;

– 50-59 years old – 28 cases – 17.5%;

– 60-69 years old – 30 cases – 18.75%;

– 70 years and over – 6 cases – 3.75%.

Fig. 3: Age distribution of the patients with sporadic goiter from the study group.

Associations between sporadic goiter with other pathologies included:

– seropositive rheumatoid arthritis – 6 cases;

– acrocyanosis – 2 cases;

– osteopenia – 2 cases;

– adrenal insufficiency – 2 cases;

– manifest tetany – 56 cases;

– hypercholesterolaemia – 16 cases;

– tumors – 36 case, from which:

– cutaneous hemangioma – 2 cases;

– bilateral mammary dysplasia – 14 cases;

– malignant lymphoma with lymphocyte predominance – 2 case;

– uterine fibroids – 10 cases;

– uterine cervical cancer – 2 cases;

– ovarian cyst – 2 cases;

– intraductal breast papilloma – 2 cases;

– hepatic hemangioma – 2 cases;

– obesity – 2 cases;

–iron deficiency anemia – 4 cases;

–cirrhosis of the liver – 2 cases;

–hyperprolactinemia – 2 cases;

– pulmonary tuberculosis – 2 cases.

Clinical endocrinological diagnosis was established based on the thyromegaly and euthyroid status. Neuropsychiatric manifestations seen in patients with goiter from the study group included:

1. Psychiatric accuses: 63 cases – 39.37% (fig. 4).

Psychiatric disorders encountered in the study group included somatization disorders with dissociative symptoms, somatoform disorders, conversive disorders, anxiety and depression syndromes, relatively common in patients with euthyroid goiter.

Fig. 4: Number of cases with psychiatric disorders out of all the cases with euthyroid goiter.

Left transient paresthesia syndromes were common and of functional nature:

– Conversive disorders – 4 cases – 2.5%;

– Anxiety disorders – 4 cases -2.5%;

– Somatization disorders with dissociative symptoms – 2 cases – 1.25%;

– Depression episodes – 4 cases – 2.5%;

– Sleep disorders: sleepiness – 8 cases – 5%; insomnia – 11 cases – 6.87%;

– Adynamia, fatigue – 10 cases – 6.25%;

– Sensations of suffocating “lump in throat” – 25 cases – 15%;

– Physical asthenia – 34 cases – 21.25%;

– Irritability, nervousness, psychomotor agitation, emotional liability – 10 cases – 6.25%;

– Repeated left hemibody paresthesia that involved performing Doppler examinations – ECD and

TCD and CT brain with results within the normal range interpreted as being improved and functional under treatment with anxiolytics: 4 cases, 2.5%;

2. Headaches: 52 cases – 32.5%;

– Diffuse headache – 50 cases – 31.25% – of which 10 cases rebellious to treatment imposed cerebral CT evaluation, which was, in all cases, within normal limits;

– Classic migraine- 2 cases – 1.25%;

3. Vertigo – 38 cases – 23.75% and unsystematic balance disorders – 8 cases – 5%

4. Fainting – 6 cases – 3.75% and syncope – 4 cases – 2.5%;

The patients with syncope were initially addressed to the neurology service for the loss of consciousness, the clinical exam detecting goiter and endocrinological evaluation – confirming euthyroid goiter with spasmophilia.

5. Tremor – 6 cases – 3.75%.

– Essential type tremor in the upper limbs – 2.5%;

– Extrapyramidal type tremor – 2 cases – 1.25%;

6. Disorders regarding the compression of the neurovascular package situated at the cervical level, as well as for trachea, esophagus with dysphonia, dyspnea, vertigo, headache, balance disorders, swallowing disorders, “lump in throat”, suffocation – 10 cases – 6.25%.

7. Muscular cramps – 2 cases – 1.25%;

8. Osteotendinous hyperrelfexia – 2 cases – 1.25%.

9. Essential trigeminal neuralgia – 1 case – 0.625%.

10. Clinically confirmed sensory neuropathy with disorders of superficial and profound sensory disorders in the lower limbs – 2 cases – 1.25%.

11. Stroke – 9 cases -5.62% (Fig 5);

– Hemorrhagic stroke – 3 cases – 1.875%;

– Ischemic – 5 cases – 3.125%;

– Ischemic transitory stroke – 3 cases – 1.875%;

– Pseudobulbar affect – 2 cases – 1.25%;

Fig 5. The prevalence of stroke in patients with euthyroid goiter from the study group.

12. Neurofibromatosis – 1 case – 0.625%;

13. Ocular myasthenia gravis – 2 cases – 1.25%: patients hospitalized with diplopia, bilateral exophthalmic thyromegaly known with ocular myasthenia gravis;

14. Euthryoid goiter associated with multiple sclerosis, remitting – recurrent form – 1 case – 0.625%;

15. Associations between euthyroid goiter, myasthenia gravis, rheumatoid arthritis, systemic vasculitis with secondary neuropathy – 1 case – 0.625%;

16. Of the 160 of goiter from the study group we encountered 4 cases of bulky thyromegaly, of which:

– 2 cases of cervical-thoracic goiter;

– 2 cases of retrosternal goiter;

We found that in all four cases the patients initially presented themselves in the neurology service for compressive phenomena which caused vertigo, dyspnea, balance disorders, dysphonia, suffocation and “lump in throat”.

– 1 case of recurrent endothoracic plunging goiter.

The diagnosis was clinically and paraclinically confirmed through mediastinum radiography, mediastinum CT, thyroid scintigram. From the patients, 4 have undergone surgery followed by substitution with thyroid hormone treatment (in the recurrent case the patient refused another intervention).

On the subsequent checks that occurred every 3 months the evolution was favorable in all 4 cases, the initial signs and symptoms disappearing completely.

Patient S.M, 46 years old:

Grounds admission: vertigo, headache, balance disorders, swallowing disorders, suffocation, “lump in throat”.

Personal history: unimportant.

Clinical exam: lowering of the soft palate on the

right side; thyromegaly grade II.

Laboratory exam: T3 – 78.9ng/dl, T4 – 10.2μg/

ml, TSH – 2.12microm/ml.

Thyroid ultrasound: both thyroid lobes were

increased in size, homogeneous structure.

Thyroid scintigraphy (fig 6):

Fig 6. Thyroid scinitgraphy – patient M.S. 46 years old – “cold” areas at the lower pole of the projection area of the right thyroid lobe.

Thoracic mediastinum CT (fig. 7):

Fig. 7: Thoracic mediastinum CT – patient S.M., 46 years old – intrathoracic tumor 7cm wide with multinodular structure, located paratracheal right, that compresses the trachea extrinsic. There are no encountered mediastinum adenopathies nor in the pulmonary hilum.

Histopathologic exam of the surgical excision piece:

Thyroid biopsy, OC x 10 x 40 OB, coloring H.E, fig.8:

Fig. 8: Thyroid microscopic aspect, OC x 10, OB x 40, coloring H.E.

Anizofollicular aspect, epithelial hyperactivity is highlighted, with maximum use of the colloid; The follicles have different sizes, some of them being cystic dilated; thyroid vesicles are much wider and thyroid cells are flattened, the colloid is homogeneous, intensely colored.

Paraclinically the endocrinological diagnosis of sporadic euthyroid goiter was established by:

– Hormonal dosages;

– Thyroid ultrasound (fig. 9):

Fig. 9: Thyroid ultrasound: Patient S.F. – 46 years old.

The size of the left thyroid lobe is 36/28mm, occupied entirely by a homogenous formation, with echoic aspect of multicystic conglomerate, with more than one septum. Isthmus has a size of 7mm. The right thyroid lobe is occupied by nodular structures, the biggest one being located median, with a diameter of 14 mm.

– Thyroid scintigraphy: examples fig. 10, 11,12.

Fig. 10: Thyroid scintigraphy – patient D.A., 55 years old – projection areas of the thyroid lobes are increased, with a hypocaptation area (“cold” nodule) in the lower 1/3 of the left lobe. Inhomogeneous capture on the projection area of theright thyroid lobe.

Fig. 11: Thyroid scintigraphy – patient S.F., 46 years old – projection areas of the thyroid lobes greatly increased, especially on the right one, irregularly shaped. Very inhomogeneous thyroid capture with delimitation of several hypocaptation areas (“cold” nodules), the largest portion in the middle part of the right thyroid lobe.

Fig. 12: Thyroid scintigraphy – patient C.V., 43 years old – the projection area of the left thyroid lobe is moderately increased. Inhomogeneous capture in both lobes, sketching a hypocaptation area in the left lobe, in the inferior – exterior side, and the small area of hypocaptation in the lower pole of the right lobe.

– histopathological examination of the surgical excision parts in the patients on which there was practiced a thyroidectomy.

These investigations have been exemplified above.

The paraclinical neurological diagnosis included:

– FO exam;

– Electromyographic examination;

– Neuroimaging CT examination;

In the study group we encountered associations of signs of hyperprolactinemia (galactorrhea), with elevated values of PRL prolactin – 52.2 ng/dl, with rebellious headache to treatment and volimunous goiter, which raised the suspicion of pituitary adenoma. Brain CT disconfirmed the diagnosis.

In 6 of the cases with persisting vertigo and balance disorders without response to treatment, a brain CT was carried out which detected a diffuse cerebral and cerebellar atrophy.

Cases of training headache associated with vertigo and thyromegaly have been evaluated through brain CT without detecting any changes in the brain.

Also, brain CT was performed for sensory syndromes in a hemicord with prolonged evolution, detecting only cortical atrophy.

Neuroimaging evaluation was imposed for the association of thyro-ovarian failure with training headache, galactorrhea and fainting, with a suspicion of pituitary adenoma, but it had not been confirmed by the brain CT. In one case with normal prolactin levels, headache, goiter and galactorrhea the diagnosis in the end was of intraductal breast papilloma.

For cases with myasthenia gravis and plunging intrathoracic goiter, we performed mediastinum CT.

Also, CT examination was performed in cases of stroke and in cases which required the study of the orbit and exophthalmometry.

CONCLUSIONS

A number of patients with euthyroid goiter presented themselves initially in the neurology service especially patients with episodes of loss of consciousness, chronic headache or vertigo and their examination led to further investigations on the endocrine line.

Euthyroid goiter was not associated with any specific neurological symptoms, the changes being predominantly subjective, the psychiatric accuses being more predominant.

The persistence of some subjective accuses such as vertigo and headache have required neuroimaging investigations.

Clinical symptoms that haven’t been disconfirmed by laboratory examination have improved after treatment with potassium iodide and symptomatic treatment.

In cases with bulky goiter or endothoracic goiter we encountered compression phenomena of the mediasinum structures or of the cervical neurovascular package.

In some situations we have registered cases of diplopia with unclear etiology, without it belonging to a neurological cause or an endocrinological one because we could not establish it with certainty. We call that diplopia may precede with a few years the installation of thyroid disorders.

We were not able to establish a direct cause or link between the two conditions, we have encountered associations between euthyroid goiter and myasthenia gravis, multiple sclerosis, neurofibromatosis and stroke.

ABBREVIATIONS

CPK-creatine phosphokinase

FT3-free serum triiodothyronine

FT4-free serum thyroxine

H.E.-hematoxylin eosin staining

LCR- cerebrospinal fluid

T3- triiodothyronine

T4- thyroxine

TcO- technetium isotope

TSH-adenohypophysis thyrotropin hormone

VCM-motor conducting velocity

VCS-sensory conducting velocity

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