Signs And Symptoms Of Graves' Disease
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The signs and symptoms of Graves' disease generally result from the direct and indirect effects of
hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
; sometimes they are caused by thyroidal conditions, such as
Graves' ophthalmopathy Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and b ...
,
goitre A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
and
pretibial myxedema Pretibial myxedema (myxoedema in British English, also known as Graves' dermopathy, thyroid dermopathy, Jadassohn-Dösseker disease or myxoedema tuberosum) is an infiltrative dermopathy, resulting as a rare complication of Graves' disease, with a ...
. These clinical manifestations can involve virtually every system in the body. The mechanisms that mediate these effects are not well understood. The severity of the signs and
symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...
s of hyperthyroidism is related to the duration of the disease, the magnitude of the thyroid hormone excess, and the patient's age. Although the vast majority of patients enjoy significant improvement and remission after proper medical care, health care providers should be aware of variability in the individual response to hyperthyroidism and individual sensitivity to thyroid hormone fluctuations generally. Graves' disease patients can also undergo periods of
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
(inadequate production of thyroid hormone; see symptoms of hypothyroidism), due to the challenges of finding the right dosage of thyroid hormone suppression and/or supplementation. The body's need for thyroid hormone can also change over time, such as in the first months after radioactive iodine treatment (RAI). Thyroid autoimmune diseases can also be volatile: hyperthyroidism can interchange with hypothyroidism and euthyroidism.Psychische stoornissen bij endocriene zieken, 1983, C. van der Meer en W. van Tilburg (red.)


General symptoms

*
Goitre A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is ...
(enlarged thyroid). If the thyroid grows large enough, it may compress the
recurrent laryngeal nerve The recurrent laryngeal nerve (RLN) is a branch of the vagus nerve (cranial nerve X) that supplies all the intrinsic muscles of the larynx, with the exception of the cricothyroid muscles. There are two recurrent laryngeal nerves, right and le ...
, producing
vocal cord paralysis Vocal cord paresis, also known as recurrent laryngeal nerve paralysis or vocal fold paralysis, is an injury to one or both recurrent laryngeal nerves (RLNs), which control all intrinsic muscles of the larynx except for the cricothyroid muscle. The ...
,
dysphonia A hoarse voice, also known as dysphonia or hoarseness, is when the voice involuntarily sounds breathy, raspy, or strained, or is softer in volume or lower in pitch. A hoarse voice, can be associated with a feeling of unease or scratchiness in the ...
, and even respiratory
stridor Stridor (Latin for "creaking or grating noise") is a high-pitched extra-thoracic breath sound resulting from turbulent air flow in the larynx or lower in the bronchial tree. It is different from a stertor which is a noise originating in the pha ...
. Compression of the
sympathetic chain The sympathetic trunks (sympathetic chain, gangliated cord) are a paired bundle of nerve fibers that run from the base of the skull to the coccyx. They are a major component of the sympathetic nervous system. Structure The sympathetic trunk lies j ...
may result in
Horner's syndrome Horner's syndrome, also known as oculosympathetic paresis, is a combination of symptoms that arises when a group of nerves known as the sympathetic trunk is damaged. The signs and symptoms occur on the same side (ipsilateral) as it is a lesion o ...
. *
Graves' ophthalmopathy Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and b ...
(protrusion of one or both eyes) *
Pretibial myxedema Pretibial myxedema (myxoedema in British English, also known as Graves' dermopathy, thyroid dermopathy, Jadassohn-Dösseker disease or myxoedema tuberosum) is an infiltrative dermopathy, resulting as a rare complication of Graves' disease, with a ...
* Cardiovascular features may include
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, and heart rate that may be
rapid Rapids are sections of a river where the river bed has a relatively steep gradient, causing an increase in water velocity and turbulence. Rapids are hydrological features between a ''run'' (a smoothly flowing part of a stream) and a ''cascade''. ...
or irregular in character; these may be perceived as
palpitations Palpitations are perceived abnormalities of the heartbeat characterized by awareness of cardiac muscle contractions in the chest, which is further characterized by the hard, fast and/or irregular beatings of the heart. Symptoms include a rapi ...
."Graves' Disease and the Manifestations of Thyrotoxicosis" – Leslie l. De Groot, Thyroid Disease Manager, Chapter 10 (http://www.thyroidmanager.org/chapter/graves-disease-and-the-manifestations-of-thyrotoxicosis/) Less common findings include
left ventricular hypertrophy Left ventricular hypertrophy (LVH) is thickening of the heart muscle of the left ventricle of the heart, that is, left-sided ventricular hypertrophy and resulting increased left ventricular mass. Causes While ventricular hypertrophy occurs na ...
, premature atrial and ventricular contractions, atrial fibrillation,
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
,
angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...
,
myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
, systemic embolization, death from
cardiovascular collapse Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...
and resistance to some drug effects (
digoxin Digoxin (better known as Digitalis), sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is on ...
,
coumadin Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to prevent blood clots such as deep vein thrombosis and pulmonary embolism, and to prevent strok ...
). *
Hyperreflexia Hyperreflexia is overactive or overresponsive bodily reflexes. Examples of this include twitching and spastic tendencies, which indicate upper disease of the upper motor neurons and the lessening or loss of control ordinarily exerted by highe ...
, with a rapid relaxation phase. * A distinctly excessive reaction to all sorts of stimuli. * A marked increase in fatigability, or
asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
, is often prominent. This increased weariness may be combined with
hyperactivity Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
; patients remark that they are impelled to incessant activity, which, however, causes great fatigue. *
Insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
*
Tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
(usually fine shaking; tremor of the outstretched fingers). In a small study of newly diagnosed hyperthyroid patients, tremor was observed in 76% of them. Some studies lay the cause for hyperthyroid tremor with a heightened beta-adrenergic state, others suggest an increased metabolism of
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...
. *
Weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...
despite normal or increased appetite. Some patients (especially younger ones) ''gain'' weight due to excessive appetite stimulation that exceeds the weight loss effect. *
Increased appetite Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to ...
. *
Weakness Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
or
muscle weakness Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, includi ...
(especially in the large muscles of the arms and legs). This latter occurs in 60 to 80 percent of patients with untreated hyperthyroidism. Muscle weakness is rarely the chief complaint. The likelihood and degree of muscle weakness is correlated with the duration and severity of the hyperthyroid state, and becomes more likely after the age of 40. Muscle strength returns gradually over several months after the hyperthyroidism has been treated. * Muscle degeneration *
Shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
* Increased sweating *
Heat intolerance Heat intolerance is a symptom characterized by feeling ''overheated'' in ''warm'' environments or when the surrounding environment's temperature rises. Typically, the person feels uncomfortably hot and sweats excessively. Compared to heat ill ...
* Warm and moist skin * Thin and fine hair * Redness of the elbows is frequently present. It is probably the result of the combination of increased activity, an exposed part, and a hyperirritable
vasomotor system Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...
. * Chronic
sinus infections Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, headac ...
* Brittle nails *
Plummer's nail Plummer's nail is a clinical sign in which there is onycholysis, or separation of the nail from the nail bed, particularly affecting the ring and little fingers. It occurs in patients with thyrotoxicosis. About 5% of hyperthyroid patients display ...
* Abnormal breast enlargement in men * Gastrointestinal symptoms. This includes increased bowel movements, but malabsorption is unusual. * Augmented calcium levels in the blood (by as much as 25% – known as
hypercalcaemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia ...
). This can cause stomach upset, excessive urination, and impaired kidney function. *
Diabetes Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
may be activated or intensified, and its control worsened. The diabetes is ameliorated or may disappear when the thyrotoxicosis is treated. * Evidence of mild or severe liver disease may be found. * Reproductive symptoms in men may include reduced free
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
(due to the elevation of testosterone-estrogen binding globulin level), diminished
libido Libido (; colloquial: sex drive) is a person's overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act up ...
,
erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...
and (reversible) impaired sperm production with lower mean sperm density, a high incidence of sperm abnormalities, and reduced mobility of the sperm cells. Women may experience infrequent menstruation or irregular and scant menstrual flow along with difficulty conceiving,
infertility Infertility is the inability of a person, animal or plant to reproduce by natural means. It is usually not the natural state of a healthy adult, except notably among certain eusocial species (mostly haplodiploid insects). It is the normal state ...
and recurrent
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
. * Neurological seizures,
neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...
from nerve entrapment by lesions of pretibial myxedema, and
hypokalemic periodic paralysis Hypokalemic periodic paralysis (hypoKPP), also known as familial hypokalemic periodic paralysis (FHPP), is a rare, autosomal dominant channelopathy characterized by muscle weakness or paralysis when there is a fall in potassium levels in the blood ...
may occur.
Athetoid Athetosis is a symptom characterized by slow, involuntary, convoluted, writhing movements of the fingers, hands, toes, and feet and in some cases, arms, legs, neck and tongue. Movements typical of athetosis are sometimes called ''athetoid'' moveme ...
,
choreia Choreia ( grc, χορεία) is a circle dance accompanied by singing (see Greek chorus, ''choros''), in ancient Greece. Homer refers to this dance in his epic poetry, epic poem, the ''Iliad''. Cognate, Cognates of ''choreia'' are used for circle ...
, and corticospinal tract damage, are rare. An acute thyrotoxic
encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
is very rare.


Effects on the skeleton

Overt hyperthyroidism caused by Grave's Disease is associated with accelerated
bone remodeling Bone remodeling (or bone metabolism) is a lifelong process where mature bone tissue is removed from the skeleton (a process called ''bone resorption'') and new bone tissue is formed (a process called ''ossification'' or ''new bone formation''). T ...
(resulting in increased porosity of
cortical bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and ...
and reduced volume of
trabecular bone A trabecula (plural trabeculae, from Latin for "small beam") is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has ...
). This can lead to reduced
bone density Bone density, or bone mineral density, is the amount of bone mineral in bone tissue. The concept is of mass of mineral per volume of bone (relating to density in the physics sense), although clinically it is measured by proxy according to optica ...
and eventually
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
as well as increased
fracture Fracture is the separation of an object or material into two or more pieces under the action of stress. The fracture of a solid usually occurs due to the development of certain displacement discontinuity surfaces within the solid. If a displa ...
rates. The increased hip fracture rates later in life in turn cause excess late mortality. The changes in bone metabolism are connected with negative calcium balance, an increased excretion of
calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
and
phosphorus Phosphorus is a chemical element with the symbol P and atomic number 15. Elemental phosphorus exists in two major forms, white phosphorus and red phosphorus, but because it is highly reactive, phosphorus is never found as a free element on Ear ...
in the urine (
hypercalciuria Hypercalciuria is the condition of elevated calcium in the urine. Chronic hypercalciuria may lead to impairment of renal function, nephrocalcinosis, and chronic kidney disease. Patients with hypercalciuria have kidneys that put out higher levels ...
) and stool, and, rarely,
hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemi ...
. In
hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
, the normal cycle duration of
bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nucleated ...
of approximately 200 days is halved, and each cycle is associated with a 9.6 percent loss of mineralized
bone A bone is a Stiffness, rigid Organ (biology), organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red blood cell, red and white blood cells, store minerals, provid ...
. In
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
, cycle length approximates 700 days and is associated with a 17 percent increase in mineralized bone. The extent of the reduction in bone density in most studies is 10–20%. The clinical manifestations on bone differ depending on the age of the patient. Postmenopausal woman are most sensitive to accelerated bone loss from thyrotoxicosis. Accelerated bone growth in growing children can increase
ossification Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in t ...
in the short term, but generally results in short-stature adults compared with the predicted heights. If thyrotoxicosis is treated early, bone loss can be minimized. The level of calcium in the blood can be determined by a simple blood test, and a Dual Energy X-Ray Absorptiometry scan can help determine patient bone density relative to the rest of the population. There are many medications that can help to rebuild bone mass and to prevent further bone loss, such as
Bisphosphonate Bisphosphonates are a class of drugs that prevent the loss of bone density, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they ...
s.
Risedronate Risedronic acid, often used as its sodium salt risedronate sodium, is a bisphosphonate. It slows down the cells which break down bone. It's used to treat or prevent osteoporosis, and treat Paget's disease of bone. It is taken by mouth. It was pa ...
treatment has been demonstrated to help restore bone mass in
osteopenia Osteopenia, known as "low bone mass" or "low bone density", is a condition in which bone mineral density is low. Because their bones are weaker, people with osteopenia may have a higher risk of fractures, and some people may go on to develop osteop ...
/
osteoporosis Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to bone fragility, and consequent increase in fracture risk. It is the most common reason for a broken bone ...
associated with Graves' disease.Chapter 11. Diagnosis and Treatment of Graves' Disease Leslie J. De Groot, MD Professor of Medicine – http://www.thyroidmanager.org/chapter/diagnosis-and-treatment-of-graves-disease/ Updated: March 5, 2008 Nevertheless, weight-bearing
exercises Exercise is a body activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons, to aid growth and improve strength, develop muscles and the cardiovascular system, hone athletic s ...
, a
balanced diet A healthy diet is a diet that maintains or improves overall health. A healthy diet provides the body with essential nutrition: fluid, macronutrients such as protein, micronutrients such as vitamins, and adequate fibre and food energy. A healt ...
, calcium intake of about 1500 mg a day and enough
vitamin D Vitamin D is a group of fat-soluble secosteroids responsible for increasing intestinal absorption of calcium, magnesium, and phosphate, and many other biological effects. In humans, the most important compounds in this group are vitamin D3 (c ...
, are of course elementary foundations.


Eye symptoms

Hyperthyroidism almost always causes general eye symptoms like dryness and irritation, regardless of what the cause of the hyperthyroid state is. However, these need to be distinguished from
Graves' ophthalmopathy Graves’ ophthalmopathy, also known as thyroid eye disease (TED), is an autoimmune inflammatory disorder of the orbit and periorbital tissues, characterized by upper eyelid retraction, lid lag, swelling, redness (erythema), conjunctivitis, and b ...
, which can only occur in patients who have Graves' disease. (It may also, rarely, be seen in
Hashimoto's thyroiditis Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis and Hashimoto's disease, is an autoimmune disease in which the thyroid gland is gradually destroyed. Early on, symptoms may not be noticed. Over time, the thyroid may enlarg ...
, primary
hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...
, and
thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...
). About 20–25% of patients with Graves' disease will suffer from clinically obvious Graves' ophthalmopathy, and not just from the eye signs of hyperthyroidism. Only 3 to 5% will develop severe ophthalmopathy. However, when subjected to closer inspection (e.g. by
magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...
of the
orbits In celestial mechanics, an orbit is the curved trajectory of an object such as the trajectory of a planet around a star, or of a natural satellite around a planet, or of an artificial satellite around an object or position in space such as a p ...
) many more patients have evidence of ophthalmopathy. It is estimated that for every 100,000 persons, 16 women and 3 men have Graves' ophthalmopathy every year. Although it is true that in most patients ophthalmopathy, goiter, and symptoms of thyrotoxicosis appear more or less coincidentally, it is also true that in certain cases eye signs may appear long before thyrotoxicosis is evident, or become worse when the thyrotoxicosis is subsiding or has been controlled by treatment. In approximately 20% of ophthalmopathy patients, ophthalmopathy appears before the onset of hyperthyroidism, in about 40% concurrently, and in about 20% in the six months after diagnosis. In the remainder, the eye disease first becomes apparent after treatment of the hyperthyroidism, more often in patients treated with radioiodine. It can sometimes be difficult to distinguish between eye symptoms due to hyperthyroidism and those due to Graves' antibodies, because the two often occur coincidentally. What can make things particularly difficult, is that many patients with hyperthyroidism have lid retraction, which leads to stare and lid lag (due to contraction of the
levator palpebrae The levator palpebrae superioris ( la, elevating muscle of upper eyelid) is the muscle in the orbit that elevates the upper eyelid. Structure The levator palpebrae superioris originates from inferior surface of the lesser wing of the sphenoid bon ...
muscles of the eyelids). This stare may then give the ''appearance'' of protruding eyeballs (
proptosis Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
), when none in fact exists. This subsides when the hyperthyroidism is treated.


Due to Graves' ophthalmopathy

Graves' ophthalmopathy is characterized by inflammation of the
extraocular muscles The extraocular muscles (extrinsic ocular muscles), are the seven extrinsic muscles of the human eye. Six of the extraocular muscles, the four recti muscles, and the superior and inferior oblique muscles, control movement of the eye and the ot ...
, orbital fat and connective tissue. It results in the following signs, which can be extremely distressing to the patient: * Most frequent are symptoms due to
conjunctival The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium an ...
or
cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
l irritation: burning,
photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...
, tearing, pain, and a gritty or sandy sensation. * Protruding eyeballs (known as
proptosis Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
and
exophthalmos Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
). *
Diplopia Diplopia is the simultaneous perception of two images of a single object that may be displaced horizontally or vertically in relation to each other. Also called double vision, it is a loss of visual focus under regular conditions, and is often v ...
(double vision) is common. * Limitation of eye movement (due to impairment of
eye muscle The extraocular muscles (extrinsic ocular muscles), are the seven extrinsic muscles of the human eye. Six of the extraocular muscles, the four recti muscles, and the superior and inferior oblique muscles, control movement of the eye and the o ...
function). * Periorbital and conjunctival
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
(accumulation of fluid beneath the skin around the eyes). * In severe cases, the
optic nerve In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...
may be compressed and acuity of vision impaired. * Occasionally
loss of vision Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individual's better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment ...
.


Due to hyperthyroidism

In the absence of Graves' ophthalmopathy, patients may demonstrate other ophthalmic symptoms and signs due to hyperthyroidism: * Dry eyes (due to loss of corneal moisture). * A sense of irritation, discomfort, or pain in the eyes. * A tingling sensation behind the eyes or the feeling of grit or sand in the eyes. * Excessive tearing that is often made worse by exposure to cold air, wind, or bright lights. * Swelling or redness of the eyes. * Stare * Lid lag (
Von Graefe's sign Von Graefe's sign is the lagging of the upper eyelid on downward rotation of the human eye, eye, indicating exophthalmos, exophthalmic Goitre, goiter (Graves' disease).Cline D; Hofstetter HW; Griffin JR. ''Dictionary of Visual Science''. 4th ed. Bu ...
) * Sensitivity to light * Blurring of vision * Widened
palpebral fissures The palpebral fissure is the elliptic space between the medial and lateral canthi of the two open eyelids. In simple terms, it is the opening between the eyelids. In adult humans, this measures about 10 mm vertically and 30 mm horizontally. Var ...
* Infrequent blinking * The appearance of lid retraction.


Neuropsychological manifestations

Several studies have suggested a high prevalence of
neuropsychiatric disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
s and
mental disorder A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...
symptoms in Graves' disease (and thyroid disease in general), which are similar to those in patients with organic brain disease. These manifestations are diverse, affecting the
central Central is an adjective usually referring to being in the center of some place or (mathematical) object. Central may also refer to: Directions and generalised locations * Central Africa, a region in the centre of Africa continent, also known as ...
and
peripheral A peripheral or peripheral device is an auxiliary device used to put information into and get information out of a computer. The term ''peripheral device'' refers to all hardware components that are attached to a computer and are controlled by the ...
nervous systems. The vast majority of patients with hyperthyroidism meet criteria for some psychiatric disorders, and those with milder presentations are probably not entirely free of mental symptoms such as emotional lability, tension, depression and anxiety. Anxiety syndromes related to hyperthyroidism are typically complicated by major depression and cognitive decline, such as in memory and attention. Some studies contradict the psychological findings. For example, a large 2002 study found "no statistical association between thyroid dysfunction, and the presence of depression or anxiety disorder." In one study on hospitalised elderly patients, over half had cognitive impairment with either dementia or confusion. However, a controlled study on 31 Graves' disease patients found that while patients had subjective reports of cognitive deficits in the toxic phase of Graves' thyrotoxicosis, formal testing found no cognitive impairment and suggested the reported symptoms may reflect the affective and somatic manifestations of hyperthyroidism. Notably, a literature review of 2006 notes
methodology In its most common sense, methodology is the study of research methods. However, the term can also refer to the methods themselves or to the philosophical discussion of associated background assumptions. A method is a structured procedure for bri ...
issues in the consistency of Graves' disease
diagnostic criteria Medical diagnosis (abbreviated Dx, Dx, or Ds) is the process of determining which disease or condition explains a person's symptoms and signs. It is most often referred to as diagnosis with the medical context being implicit. The information req ...
, which might explain the apparently contradicting findings. These researchers found many reports about residual complaints in patients who were euthyroid after treatment, with a high prevalence of
anxiety disorders Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
and
bipolar disorder Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
, as well as elevated scores on scales of
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, depression and psychological distress. In a 1992 study, a significant proportion of the 137 questioned patients with Graves' disease reported – among other things – increased crying (55%), being easily startled (53%), being tired all the time (47%), a significant decrease in social activity (46%), feelings of being out of control (45%), feelings of hopelessness (43%), loss of sense of humor (41%), loss of interest in things they formerly enjoyed (39%), not being able to 'connect' with others (34%). Several studies point out that the severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism. Consequently, undiagnosed hyperthyroidism sometimes results in inappropriate use of psychotropic medications; prompt recognition of hyperthyroidism (or hypothyroidism) through thyroid function screening is therefore recommended in the evaluation of patients with psychiatric symptoms. Naturally, the management of patients would be improved by collaboration between an
endocrinologist Endocrinology (from ''endocrine'' + '' -ology'') is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions known as hormones. It is also concerned with the integration of developmental events ...
and a
psychiatrist A psychiatrist is a physician who specializes in psychiatry, the branch of medicine devoted to the diagnosis, prevention, study, and treatment of mental disorders. Psychiatrists are physicians and evaluate patients to determine whether their sy ...
. Overall, reported symptoms vary from mild to severe aspects of anxiety or depression, and may include psychotic and behavioral disturbances: * Varying degrees of
anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...
, such as a very active mind,
irritability Irritability (also called as crankiness) is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessi ...
,
hyperactivity Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
, agitation, restlessness,
nervousness Nervous may refer to: * nervousness * Nervous system, a network of cells in an animal's body that coordinates movement and the senses ** Nervous tissue, the cells of the nervous system that work in aggregate to transmit signals Music * "Nervous" ...
, distractible hyperactivity and
panic attacks Panic attacks are sudden periods of intense fear and discomfort that may include palpitations, sweating, chest pain or chest discomfort, shortness of breath, trembling, dizziness, numbness, confusion, or a feeling of impending doom or of losing ...
. In addition patients may experience vivid dreams and, occasionally,
nightmares A nightmare, also known as a bad dream, Retrieved 11 July 2016. is an unpleasant dream that can cause a strong emotional response from the mind, typically fear but also despair, anxiety or great sadness. The dream may contain situations of d ...
. * Depressive features of mental impairment, memory lapses, diminished attention span, fluctuating depression. *
Emotional lability In medicine and psychology, emotional lability is a sign or symptom typified by exaggerated changes in mood or affect in quick succession. Sometimes the emotions expressed outwardly are very different from how the person feels on the inside. Thes ...
and in some patients
hypomania Hypomania (literally "under mania" or "less than mania") is a mental and behavioural disorder, characterised essentially by an apparently non-contextual elevation of mood (euphoria) that contributes to persistently disinhibited behaviour. The ...
. * The pathological well-being (
euphoria Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...
) or hyperactivity may produce a state of exhaustion, and profound fatigue or
asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...
chiefly characterizes the picture. * Erratic behaviour may include intermittent rage disorder and mild attention deficit disorder. Some patients become hyperirritable and combative, which can precipitate accidents or even assaultive behaviour. * In more extreme cases features of
psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...
, with delusions of persecution or
delusions of reference Ideas of reference and delusions of reference describe the phenomenon of an individual experiencing innocuous events or mere coincidences and believing they have strong personal significance. It is "the notion that everything one perceives in the ...
, and
pressure of speech Pressure of speech or pressured speech is a tendency to speak rapidly and frenziedly. Pressured speech is motivated by an urgency that may not be apparent to the listener. The speech produced is difficult to interpret. Such speech may be too fas ...
may present themselves. Rarely, patients develop visual or auditory
hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...
or a frank psychosis, and may appear
schizophrenic Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
, lose touch with reality and become delirious, Such psychotic symptoms may not completely clear up after the hyperthyroidism has been treated. Paranoia and paranoid-hallucinatory psychosis in hyperthyroidism usually have a manic disposition and it is therefore often not clear if the patient is experiencing a paranoid psychosis with depressive streaks, or a depression that has paranoid streaks. Treatment of hyperthyroidism typically leads to improvement in cognitive and behavioral impairments. Agitation, inattention, and frontal lobe impairment may improve more rapidly than other cognitive functions. However, several studies confirm that a substantial proportion of patients with hyperthyroidism have psychiatric disorders or mental symptoms and decreased quality of life even after successful treatment of their hyperthyroidism.


Effects on pre-existing psychiatric disorders

Patients with pre-existing psychiatric disorders, will experience a worsening of their usual symptoms, as observed by several studies. A study of 1999 found that Graves' disease exacerbated the symptoms of
Tourette's disorder Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
and
attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...
(ADHD), and points out that the lack of diagnosis of the Graves' disease compromised the efficacy of the treatment of these disorders. Patients who are known to have a convulsive disorder may become more difficult to control with the usual medications, and seizures may appear in patients who have never previously manifested such symptoms.


Sub-clinical hyperthyroidism

In sub-clinical hyperthyroidism, serum TSH is abnormally low, but T4- and T3-levels fall within laboratory reference ranges. It primarily affects the
skeleton A skeleton is the structural frame that supports the body of an animal. There are several types of skeletons, including the exoskeleton, which is the stable outer shell of an organism, the endoskeleton, which forms the support structure inside ...
and the cardiovascular system (abnormalities in other systems have also been reported), in a similar but less severe and less frequent way than overt
hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
does. It can alter cardiac function, with
increased heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, increased
left ventricular A ventricle is one of two large chambers toward the bottom of the heart that collect and expel blood towards the peripheral beds within the body and lungs. The blood pumped by a ventricle is supplied by an atrium, an adjacent chamber in the upper ...
mass index, increased
cardiac contractility Myocardial contractility represents the innate ability of the heart muscle (cardiac muscle or myocardium) to muscle contraction, contract. The ability to produce changes in force during contraction result from incremental degrees of binding between ...
,
diastolic dysfunction Heart failure with preserved ejection fraction (HFpEF) is a form of heart failure in which the ejection fraction – the percentage of the volume of blood ejected from the left ventricle with each heartbeat divided by the volume of blood when the l ...
, and induction of ectopic atrial beats. Long-term mild excess of thyroid hormone can thus cause impaired
cardiac reserve Cardiac reserve refers to the difference between the rates at which the heart pumps blood - at any given time versus its maximum capacity. A measurement of the cardiac reserve may be a health indicator for some medical conditions. Cardiac reserve ma ...
and exercise capacity. In a large population-based study of 2008, the odds of having poorer
cognitive function Cognitive skills, also called cognitive functions, cognitive abilities or cognitive capacities, are brain-based skills which are needed in acquisition of knowledge, manipulation of information and reasoning. They have more to do with the mechanisms ...
were greater for sub-clinical hyperthyroidism than for
stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
, and
Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
. Sub-clinical hyperthyroidism might modestly increase the risk of cognitive impairment and dementia. A possible explanation for the mental symptoms of sub-clinical thyroid disease, might be found in the fact that the brain has among the highest expression of THR's, and that neurons are often more sensitive than other tissues to thyroid abnormalities, including sub-clinical hyperthyroidism and thyrotoxicosis. In a 1996 survey study respondents reported a significant decline in memory, attention, planning, and overall productivity from the period 2 years prior to Graves' symptoms onset to the period when hyperthyroid. Also, hypersensitivity of the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
to low-grade hyperthyroidism can result in an
anxiety disorder Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal function are significantly impaired. Anxiety may cause physi ...
before other Graves' disease symptoms emerge. E.g.,
panic disorder Panic disorder is a mental disorder, mental and Abnormal behavior, behavioral disease#Disorder, disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear th ...
has been reported to precede Graves' hyperthyroidism by 4 to 5 years in some cases, although it is not known how frequently this occurs. However, while clinical hyperthyroidism is associated with frank neuropsychological and affective alterations, the occurrence of these alterations and their treatment in mild and sub-clinical hyperthyroidism remains a controversial issue. Regardless of the inconsistent findings, a 2007 study by Andersen et al. states that the distinction between sub-clinical and overt thyroid disease is in any case somewhat arbitrary. Sub-clinical hyperthyroidism has been reported in 63% of euthyroid Graves' disease, but only in 4% of cases where Graves' disease was in remission.


Children and adolescents

Hyperthyroidism has unique effects in children on growth and pubertal development, e.g. causing
epiphyseal The epiphysis () is the rounded end of a long bone, at its joint with adjacent bone(s). Between the epiphysis and diaphysis (the long midsection of the long bone) lies the metaphysis, including the epiphyseal plate (growth plate). At the joi ...
maturation. In growing children, accelerated bone growth from hyperthyroidism can increase
osteogenesis Osteoblasts (from the Greek combining forms for "bone", ὀστέο-, ''osteo-'' and βλαστάνω, ''blastanō'' "germinate") are cells with a single nucleus that synthesize bone. However, in the process of bone formation, osteoblasts function ...
in the short term, but generally results in short-stature adults compared with the predicted heights. Pubertal development tends to be delayed, or slowed. Girls who have undergone
menarche Menarche ( ; ) is the first menstrual cycle, or first menstrual bleeding, in female humans. From both social and medical perspectives, it is often considered the central event of female puberty, as it signals the possibility of fertility. Gir ...
may develop secondary
amenorrhea Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
. Hyperthyroidism is associated with high sex hormone-binding globulin (
SHBG Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen-b ...
), which may result in high serum
estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...
levels in girls and
testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...
levels in boys. However, unbound or free levels of these hormones are decreased. Hyperthyroidism before the age of four may cause neurodevelopmental delay. A study by Segni et al. suggests that permanent
brain damage Neurotrauma, brain damage or brain injury (BI) is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors. In general, brain damage refers to significant, undiscriminating t ...
can occur as a result of the illness. Ophthalmopatic findings are more common but less severe in children (severe infiltrative exophthalmos is virtually unknown before mid-adolescence), but besides that, many of the typical clinical features of hyperthyroidism in children and adolescents are similar to those in adults. An important difference between children and adults with Graves' disease, is that children have not yet developed like adults have (psychological and physiological), and that they are a lot more dependent on their environment. The
encephalopathy Encephalopathy (; from grc, ἐνκέφαλος "brain" + πάθος "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but r ...
will have profound effects on children's developing personalities and developing relationship with their environment. Disturbments in bodily development further complicates matters. The consequences for the development and the somatic and psychological well-being of the child can be very radical and sometimes irreversible. The earlier a person is affected by thyroid disease, the more the development of personality is affected and the bigger the delay from their potential development level. The child gets behind in its cognitive, emotional and sexual growth, which, by itself, also influences its processing abilities of the endocrine disease. Children with hyperthyroidism tend to have greater
mood swings A mood swing is an extreme or sudden change of Mood (psychology), mood. Such changes can play a positive part in promoting problem solving and in producing flexible forward planning, or be disruptive. When mood swings are severe, they may be ...
and disturbances of behavior, as compared with adults. Their attention span decreases, they are usually hyperactive and distractible, they sleep poorly, and their school performance deteriorates. Because devastating personality and emotional changes often appear in the child or adolescent with Graves' disease, many hyperthyroid children are (similar to many adults) referred to a developmental specialist or child psychiatrist before the presence of hyperthyroidism is suspected.


Older patients

In older patients, emotional instability may be less evident, or depression may occur, and the symptoms and signs are manifestly circulatory. In many, the thyroid is not readily palpable. Symptoms such as
rapid heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
,
shortness of breath Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
on exertion, and
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
may predominate. Older patients also tend to have more weight loss and less of an increase in appetite. Thus
anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...
in this group is fairly frequent, as is
constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
. Elderly patients may have what is called "apathetic thyrotoxicosis", a state in which they have less and less severe symptoms, except for weakness, depression and
lethargy Lethargy is a state of tiredness, sleepiness, weariness, fatigue, sluggishness or lack of energy. It can be accompanied by depression, decreased motivation, or apathy. Lethargy can be a normal response to inadequate sleep, overexertion, overwo ...
(making it even more prone to escape diagnosis).


Graves' disease and work

Considering the many signs and symptoms, the generally delayed diagnosis, and the possibility of residual complaints after treatment, it is little wonder that a significant number of people with Graves' disease have difficulty keeping their job. One study found that of 303 patients successfully treated for hyperthyroidism (77% had Graves' disease) 53% dealt with lack of energy. About one-third were unable to resume their customary work, mainly due to persistent mental problems. In their 1986 study of 26 patients (10 years after successful treatment of hyperthyroidism), Perrild et al. note that four patients had been granted
disability pension A disability pension is a form of pension given to those people who are permanently or temporarily unable to work due to a disability. North America An example of a disability pension is from a private or Public Pension Plan, or the Canada Pens ...
s on the basis of intellectual dysfunction. Between 2006 and 2008, Ponto et al. surveyed 250 Graves' disease patients. Of these, 36% were written off sick and 5% even had to take
early retirement Retirement is the withdrawal from one's position or occupation or from one's active working life. A person may also semi-retire by reducing work hours or workload. Many people choose to retire when they are elderly or incapable of doing their j ...
. In the same study, 34% of 400 questioned physicians reported treating patients with fully impaired earning capacity. Patients can and do recover with appropriate therapy while continuing to work, but more rapid and certain progress is made if a period away from the usual occupation can be provided. Two important considerations are adequate rest and attention to nutrition.


References

{{reflist Symptoms and signs: Endocrinology, nutrition, and metabolism Thyroid disease Autoimmune diseases