Symptoms of toxic multinodular goitre are similar to that of hyperthyroidism, including:

- heat intolerance

- muscle weakness/wasting

- hyperactivity

- fatigue

- tremor

- irritability

- weight loss

- osteoporosis

- increased appetite

- non-painful goitre (swelling of the thyroid gland)

- tachycardia (high heart rate - above 100 beats per minute at rest in adults)

Toxic multinodular goiter (also known as toxic nodular goiter, or Plummer's disease) is a multinodular goiter associated with hyperthyroidism.

It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).

Toxic multinodular goiter is the second most common cause of hyperthyroidism (after Graves' disease) in the developed world, whereas iodine deficiency is the most common cause of hypothyroidism in developing-world countries where the population is iodine-deficient. (Decreased iodine leads to decreased thyroid hormone.) However, iodine deficiency can cause goitre (thyroid enlargement); within a goitre, nodules can develop. Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female.

Toxic nodular goiter (TNG) (or toxic multinodular goiter, or Plummer's disease) is a condition that can occur when a hyper-functioning nodule develops within a longstanding goiter. This results in hyperthyroidism, without the eye bulging effects seen in Grave's disease. These toxic nodular goiters are most common in women over the age of 60.

It was named by Henry Stanley Plummer.

Toxic nodular goiter is the presence of thyrotoxicosis and thyroid nodules. It is prevalent in people older than 40 years old who have an iodine deficiency. There is a much higher incidence of TNG in European countries in comparison to the United States. This condition is not common in the United States and Canada due to the iodine addition in table salt. Americans consume much higher dosages of iodine compared to the 25–100 ug/day that Europeans consume.

TNG is caused by a toxic multinodular goiter. Autonomous thyroid nodules become hyper-functional from mutations in the follicular cell. The mutation activates cAMP (cyclic adenosine monophosphate), causing an increase in the cells' function and growth. This is different from the thyroid condition called Grave’s disease, as Grave’s disease causes a hyper-function from external factors such as immunoglobulin that activate the TSH receptors. Hyper-function of TSH, thyroid stimulating hormone, activates the thyroid, which in excess can cause a condition known as goiter. The nodules that form could be driven by a loss of inhibition or gain of function mutations; however, this is purely speculation as the cause is still unknown. These nodules are assumed to be irreversible and when functional can lead to thyrotoxicosis (another name for hyperthyroidism).

Thyrotoxicosis has been documented to have some cases of spontaneous remission without treatment as seen in the study done by Siegel and Lee. It is possible that the remission of thyrotoxicosis is a result of spontaneous hemorrhage and cystic degeneration. This situation means that bleeding would occur in the thyroid, which could cause the nodules to break down, reversing the symptoms. These results of spontaneous remission were contrary to the study’s previous results showing that the nodules were irreversible. Patients presenting symptoms of toxic nodular goiter can also be treated using the same procedures as hyperthyroidism.

Ten (of 75) young patients had neurologic findings such as febrile seizures, single generalized seizures, mild ataxia, and muscular hypotonia with retarded motor development, but magnetic resonance imaging detected unilateral and bilateral T2-hyperintensive white-matter lesions in 15 patients (20%)

According to recent studies, calcifications of channels seen in dementia can also occur in specific brain areas such as the visual complex in the occipital lobe. Such calcium channel blockages can cause visual problems or partial field hallucinations (Paroxysmal visual manifestations). Other papers show a link between migraine, visual aura and cerebral calcifications. Disturbances may be followed by

convulsions and associated with gastrointestinal phenomena.

Symptoms are not specific; most patients report itching, burning, and soreness. A small subset of patients may be asymptomatic. Presence of vulvar pain, bleeding, and tumor formation are reported to be more common in patients affected by invasive disease.Signs and symptoms are skin lesions, often mistaken as eczema, that may be itchy or painful.

The histiocytosis of Rosai–Dorfman disease can occur in lymph nodes, causing lymphadenopathy, or can occur outside lymph nodes in extranodal disease.

Vulvar Paget disease presents as a variety of clinical lesions that may occur over a protracted course. Initially it is velvety, soft, and red or bright pink with scattered white islands of hyperkeratosis. (a strawberry and cream appearance) The lesions become erythematous, plaque like, and desquamating especially when located in dry areas. Rarely the appearance is ulcerated. The borders appear irregular, slightly elevated, and sharply demarcated. The visible borders of vulvar Paget disease are often misleading as Paget cells may spread along the basal layers of normal appearing skin with multicentric foci. Involvement may be extensive including the perianal region, genitocrural, and inguinal folds. Clinical examination should determine the presence of periurethral and perianal lesions. In these cases an involvement of the skin by a noncutaneous internal neoplasm may occur.

Minimal change disease (also known as MCD and nil disease, among others) is a disease affecting the kidneys which causes a nephrotic syndrome. Nephrotic syndrome leads to the excretion of protein, which causes the widespread oedema (soft tissue swelling) and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 3 years of age.

The most common symptoms are diarrhea, abdominal pain, weight loss, and joint pains. The joint pains may be due to migratory non-deforming arthritis, which may occur many years before any digestive tract symptoms develop; they tend to involve the large joints but can occur in any pattern and tend not to damage the joint surface to the point that the joint becomes deformed. Fever and chills occur in a small proportion of people.

In its more advanced form, malabsorption (insufficient absorption of nutrients from the diet) leads to wasting and the enlargement of lymph nodes in the abdomen. Neurological symptoms (discussed below) are more common in those with the severe form of the abdominal disease. Chronic malabsorptive diarrhea leads to the poor absorption of fat, causing steatorrhea (fatty, offensive stool), flatulence, and abdominal distension. Protein-losing enteropathy may also occur, causing depletion of albumin, a blood protein, which may lead to peripheral edema caused by the lowered oncotic pressures.

Hyperpigmentation of the skin occurs in almost half; some also have skin nodules. Various eye problems, such as uveitis, may occur; this is typically associated with deteriorating vision and pain in the affected eye. Endocarditis (infection of the heart valve) has been reported in a small number of cases, sometimes in people with no other symptoms of Whipple's disease; this is typically noticed as breathlessness and leg swelling due to fluid accumulation as the heart is unable to pump fluid through the body.

Of those affected by Whipple's disease, 10–40% of people have problems related to the involvement of the brain; the symptoms relate to the part of the brain that is affected. The most common problems are dementia, memory loss, confusion, and decreased level of consciousness. Eye movement disturbances and myorhythmia (rapidly repetitive movements of the muscles) of the face, together referred to as "oculomasticatory myorhythmia", are highly characteristic for Whipple's disease. Weakness and poor coordination of part of the body, headaches, seizures, as well as a number of more uncommon neurological features, are present in some cases.

Kyrle disease symptoms are chronic and have an onset during adulthood between the ages of 30 and 50 years of age. However, there were reported cases of early onset as early as 5 years of age and late onset as late as 75 years of age. The main symptom is the development of small papules into painless lesions that are surrounded by silvery scales. The lesions are painless, however, there is a chance that the patient may experience extreme urges to itch them. In time, these lesions grow up to a radius of 0.75 inch and develop into red-brown nodules with a central plug of keratin. As more lesions develop, they can come together and form larger keratotic plaques. These lesions are usually observed on the lower extremities, however, can also develop on the upper extremities, such as, the arms, the head and the neck. The only parts of the body that Kyrle disease do not form are the palms, soles, and mucous membranes. Lesions may heal spontaneously without treatment, however, new ones will develop in its place.

Other symptoms that may be observed:

- Hyperkeratotic cone-shaped papular plugs

- Hyperkeratotic verrucous plaques

- Diabetes mellitus

- Hepatic insufficiency

- Presence of albumin in the urine

- Excess sugar in the urine

The disease typically presents with joint pain, high fevers, a salmon-pink rash, enlargement of the liver and spleen, swollen lymph nodes, and an increased white blood cell count in the blood. Tests for rheumatoid factor and anti-nuclear antibodies are usually negative and serum ferritin is elevated. Patients experiencing a flare-up from Adult-onset Still's disease usually report extreme fatigue, swelling of the lymph nodes and, less commonly, fluid accumulation in the lungs and heart. In rare cases, AOSD can cause aseptic meningitis and sensorineural hearing loss.

Lymphadenopathy can occur in one or more groups of lymph nodes. Among 358 cases of Rosai–Dorfman disease that Rosai collected in a disease registry for which the location of lymphadenopathy was specified, 87.3% had cervical lymphadenopathy. Axillary, inguinal, and mediastinal lymphadenopathy are also found in Rosai–Dorfman disease.

Four cardinal symptoms have sometimes been used as diagnostic criteria:

1. painful, fatty lipomas (benign fatty tumors) across anatomy

2. obesity, frequently in menopausal age

3. weakness and fatigue

4. emotional instability, depression, epilepsy, confusion, and dementia.

There are also potential signs of the disease which are identified as the following:

However, as it is unclear which symptoms are cardinal and which symptoms are minor signs in Dercum's disease, it is unclear which should be used as diagnostic criteria. Researchers have proposed a 'minimal definition' based on symptoms most often part of Dercum's disease: 1) Generalized overweight or obesity. 2) Chronic pain in the adipose tissue. The associated symptoms in Dercum's disease include obesity, fatty deposits, easy bruisability, sleep disturbances, impaired memory, depression, difficulty concentrating, anxiety, rapid heartbeat, shortness of breath, diabetes, bloating, constipation, fatigue, weakness and joint and muscle aches. Regarding the associated symptoms in Dercum's disease, only case reports have been published. No study involving medical examinations has been performed in a large group of patients.

Adult-onset Still's disease (AOSD) is a form of Still's disease, a rare systemic autoinflammatory disease characterized by the classic triad of persistent high spiking fevers, joint pain, and a distinctive salmon-colored bumpy rash. The disease is considered a diagnosis of exclusion. Levels of the iron-binding protein ferritin may be elevated with this disorder. AOSD may present in a similar manner to other inflammatory diseases and to autoimmune diseases, which must be ruled out before making the diagnosis.

Prognosis is usually favorable but manifestations of the disease affecting the lungs, heart, or kidneys may occasionally cause severe life-threatening complications. It is treated first with steroids such as prednisone. Drugs that block the action of interleukin-1, such as anakinra, can be effective treatments when standard steroid treatments are insufficient.

Signs of chronic liver disease detectable on clinical examination can be divided into those that are associated with the diagnosis of chronic liver disease, associated with decompensation and associated with the cause.

Grover's disease often starts quite suddenly. There are intensely itchy spots on the central back, mid chest and occasionally elsewhere. Frequently, it follows sweating or some unexpected heat stress.

The itchy eruption lasts an average of 10–12 months. It is characterized by papules and papulovesicles with excoriations occurring on the chest, back, lower sternum, arms, and thighs. The papules are most commonly found on the mid chest.

Sometimes the features of Grover's are found in people who do not itch or have a conspicuous rash. Most of the people with Grover's who visit a dermatologist, however, itch a lot.

Arthralgia is seen in up to half of people, and is usually a non-erosive poly or oligoarthritis primarily of the large joints of the lower extremities.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation (chronic hepatitis), liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

GI manifestations include abdominal pain, nausea, and diarrhea with or without blood, and they often involve the ileocecal valve. Many patients with BD often complain about abdominal tenderness, bloating, and generic abdominal discomfort that closely mimics irritable bowel syndrome.

Whipple's disease is a rare, systemic infectious disease caused by the bacterium "Tropheryma whipplei". First described by George Hoyt Whipple in 1907 and commonly considered a gastrointestinal disorder, Whipple's disease primarily causes malabsorption but may affect any part of the body including the heart, brain, joints, skin, lungs and the eyes. Weight loss, diarrhea, joint pain, and arthritis are common presenting symptoms, but the presentation can be highly variable and approximately 15% of patients do not have these classic signs and symptoms.

Whipple's disease is significantly more common in men, with 87% of the patients being male. When recognized and treated, Whipple's disease can usually be cured with long-term antibiotic therapy; if the disease is left untreated, it is ultimately fatal.

The clinical signs of minimal change disease are proteinuria (abnormal excretion of proteins, mainly albumin, into the urine), oedema (swelling of soft tissues as a consequence of water retention), and hypoalbuminaemia (low serum albumin). These signs are referred to collectively as nephrotic syndrome. Minimal change disease is unique among the causes of nephrotic syndrome as it lacks evidence of pathology in light microscopy, hence the name.

When albumin is excreted in the urine, its serum (blood) concentration decreases. Consequently, the intravascular oncotic pressure reduces relative to the interstitial tissue. The subsequent movement of fluid from the vascular compartment to the interstitial compartment manifests as the soft tissue swelling referred to as oedema. This fluid collects most commonly in the feet and legs, in response to gravity, particularly in those with poorly functioning valves. In severe cases, fluid can shift into the peritoneal cavity (abdomen) and cause ascites. As a result of the excess fluid, individuals with minimal change disease often gain weight, as they are excreting less water in the urine, and experience fatigue. Additionally, the protein in the urine causes it to become frothy.

PVS sufferers often complain of a burning sensation with the tongue and oral mucosa, and atrophy of lingual papillae produces a smooth, shiny, red, dorsum of the tongue. Symptoms include:

Serial contrasted gastrointestinal radiography or upper gastrointestinal endoscopy may reveal the web in the esophagus. Blood tests show a hypochromic microcytic anemia that is consistent with an iron-deficiency anemia. Biopsy of involved mucosa typically reveals epithelial atrophy (shrinking) and varying amounts of submucosal chronic inflammation. Epithelial atypia or dysplasia may be present.It may also present as a post-cricoid malignancy which can be detected by loss of laryngeal crepitus. Laryngeal crepitus is found normally and is produced because the cricoid cartilage rubs against the vertebrae.

The most common presentation of Milroy Disease is bilateral lower extremity lymphedema, and may also be accompanied by hydrocele.

Kyrle disease or hyperkeratosis follicularis et parafollicularis in cutem penetrans is identified as a form of an acquired perforating disease. Other major perforating diseases are elastosis perforans serpiginosa and reactive perforating collagenosis. Recently, however, there is a controversy on categorizing Kyrle disease with perforating dermatosis or a subtype of acquired perforating collagenosis.

Kyrle disease was first described by Josef Kyrle in 1916 when a diabetic woman presented generalized hyperkeratotic nodules. The disease is distinguished by large papules with central keratin plus on the skin, usually on the legs of the patient and is often in conjunction with hepatic, renal or diabetic disorders. It can affect both females and males with a 6:1 ratio. The papules usually show up on the patient with an average age of 30 years. Kyrle disease is a rare disease unless there is a high count of patients with chronic renal failure. The disease seems to be more prevalent in African Americans, which can be correlated to the high incidence of diabetes mellitus and renal failure in the population.