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                   ==GRAVES DISEASE AND STRESS==


Minerva Chir 1995 Jul;50(7-8):659-665

[Current trends in the treatment of Graves' disease].

[Article in Italian]

Nicolosi A, Meleddu C, Meleddu G, Massidda B, Calo PG, Pinna M, Tarquini A

Istituto di Chirurgia e Oncologia, Universita degli Studi, Cagliari.

Between 1973 and 1992 153 patients with Graves' disease were observed at
the Surgery and Oncology Institute-Cagliari University. 103 underwent
subtotal (70) or total (33) thyroidectomy, while 50(after 1985) were
submitted to radioactive-iodine therapy. Surgical indications were failure
of antithyroid drug therapy, signs of compression and large size goitre.
Until 1988, all patients were submitted to subtotal thyroidectomy with
thyroid remnant of about 8 g. From 1988 the choice of total thyroidectomy
came out from: similar complications (paralysis of recurrent nerve and
hypoparathyroidism), lack of relapse and suppression of risk of occult
carcinoma. After subtotal thyroidectomy definitive hypoparathyroidism in 1
patient (1.8%), transitory hypoparathyroidism in 5 (9.4%), clinical
hypothyroidism in 17 (31.5%), recidive hyperthyroidism in 3 patients (5.5%)
were observed. After total thyroidectomy 1 patient presented definitive
paralysis of recurrent nerve (3%), 1 definitive hypoparathyroidism (3%), 8
transitory hypoparathyroidism (24%): small (44 patients) or large goitre (3
patients) or relapse (3 patients) were indications to radioactive-iodine
therapy. At median follow-up of 16 months no relapses of hyperthyroidism
were observed, while clinical signs of hypothyroidism were present in 33%
of patients. Authors stress that, after a first attempt with antithyroid
drugs therapy, radioiodine treatment is elective in Graves' disease.
Surgery still remains the treatment of choice during pregnancy, in patients
with large goitres, signs of compression or in presence of scintigraphic
"cold" area.

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Acta Endocrinol (Copenh) 1993 Apr;128(4):293-296

Life events in the pathogenesis of Graves' disease. A controlled study.

Sonino N, Girelli ME, Boscaro M, Fallo F, Busnardo B, Fava GA

Institute of Semeiotica Medica, University of Padova, Italy.

Contradictory findings have been reported about a possible causal
relationship of life stress to Graves' disease. We evaluated this issue by
investigating the occurrence of stressful life events in the year before
the first signs of disease onset, using methods that have been found to be
valid and reliable in psychosomatic research. Seventy consecutive patients
with Graves' disease and a control group of 70 healthy subjects, matched
for sociodemographic variables, were studied. Paykel's Interview for Recent
Life Events (a semistructured research interview covering 64 life events)
was administered to patients, not during the acute phase of illness but
while on remission, by antithyroid drug treatment. Patients with Graves'
disease reported significantly more life events compared to controls (p <
0.001). They also had more independent events (p < 0.001) and events that
had an objective negative impact (p < 0.001) according to an independent
rater, unaware whether the events had occurred in patients or controls. All
categories of events were found to be significantly more frequent in
patients suffering from Graves' disease than in controls. By rigorous
methods (inclusion of patients with Graves' disease only, careful dating of
the onset of symptoms, accurate event definition, delay of the interview
upon disease remission, use of a blind rater for judging independence and
objective negative impact), our results support the concept of an excess of
life events in Graves' disease. Stressful life events may affect the
regulatory mechanisms of immune function in a number of ways. Within the
extreme complexity of the phenomena implicated in the pathogenesis of
autoimmune thyroid hyperfunction, our findings emphasize the role of
emotional stress.

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Clin Endocrinol (Oxf) 1989 Apr;30(4):429-433

Free radicals and Graves' disease: the effects of therapy.

Wilson R, Chopra M, Bradley H, McKillop JH, Smith WE, Thomson JA

University Department of Medicine, Glasgow Royal Infirmary, UK.

Plasma thiol (PSH), caeruloplasmin (CP), intracellular lysate thiol (LSH)
and superoxide dismutase (SOD) activity were measured in 30 patients with
newly diagnosed Graves' disease (GD). Compared to control subjects (C) PSH
and SOD were significantly reduced (C vs GD, 507 vs 449 mumol/l, P less
than 0.01; 2.1 vs 1.6 mumol/l, P less than 0.01 respectively) and LSH was
significantly raised (C vs GD 181 vs 298 mumol/l). Treatment with
carbimazole produced a significant rise in LSH and SOD. Propylthiouracil
(PTU) treatment raised LSH levels but 131I treatment produced no
significant change. All four parameters are involved in different ways in
oxygen metabolism and together provide an indication of oxidative stress
across the red-cell membrane. In addition LSH is a general radical
scavenger and SOD a specific O2- scavenger. In Graves' disease the
increased oxidative stress and increased general radical scavenging may
result from raised free-radical activity. These changes, which have not
previously been reported in Graves' patients, were modified by antithyroid
drug therapy, but it is not clear whether this is a direct or indirect
effect.

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J Nucl Med 1985 Jun;26(6):592-599

Correlation of stress with outcome of radioiodine therapy for Graves'
disease.

Stewart T, Rochon J, Lenfestey R, Wise P

Between November 1965 and December 1983, 293 patients were treated for
Graves' disease using 131I. All patients were asked to identify a stressful
event antedating the onset of overt clinical symptoms. Eighty-one patients
were able to do this (27.6%). Six patients were lost to follow-up, the
others were followed from 1 to 155 mo. Two hundred forty-four patients
received a single treatment, 49 required two or more treatments. Stress and
nonstress individuals were consistent with respect to age, sex, number of
treatments and the dose of radioiodine. Patients with stress initiating the
symptoms of Graves' disease became hypothyroid earlier, 50% at 12 mo
compared with 36 mo for the nonstress group, p = 0.01. At 10 yr 5% of the
stress group remained euthyroid compared with 17% nonstress. We conclude
that stress in the 12 mo or less before the onset of clinical symptoms
potentiates the development of hypothyroidism induced by a standard dose of
radioiodine.

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