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There is no known curative treatment presently. Hearing aids and cataract surgery may be of use. Control of seizures, heart failure and treatment of infection is important. Tube feeding may be needed.
The disorder is treated with vasopressin analogs such as Desmopressin. Nonetheless, many times desmopressin alone is not enough to bring under control all the symptoms, and another intervention must be implemented.
Most Cushing's syndrome cases are caused by corticosteroid medications, such as those used for asthma, arthritis, eczema and other inflammatory conditions. Consequently, most patients are effectively treated by carefully tapering off (and eventually stopping) the medication that causes the symptoms.
If an adrenal adenoma is identified, it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients require steroid replacement postoperatively at least in the interim, as long-term suppression of pituitary ACTH and normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.
In those patients not suited for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone) but they are of limited efficacy. Mifepristone is a powerful glucocorticoid type II receptor antagonist and, since it does not interfere with normal cortisol homeostatis type I receptor transmission, may be especially useful for treating the cognitive effects of Cushing's syndrome. However, the medication faces considerable controversy due to its use as an abortifacient. In February 2012, the FDA approved mifepristone to control high blood sugar levels (hyperglycemia) in adult patients who are not candidates for surgery, or who did not respond to prior surgery, with the warning that mifepristone should never be used by pregnant women.
Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation. This clinical situation is known as Nelson's syndrome.
Treatment options depend on the type of tumor and on its size:
- Prolactinomas are most often treated with cabergoline or quinagolide (both dopamine agonists), which decrease tumor size as well as alleviates symptoms, followed by serial imaging to detect any increase in size. Treatment where the tumor is large can be with radiation therapy or surgery, and patients generally respond well. Efforts have been made to use a progesterone antagonist for the treatment of prolactinomas, but so far have not proved successful.
- Somatotrophic adenomas respond to octreotide, a long-acting somatostatin analog, in many but not all cases according to a review of the medical literature. Unlike prolactinomas, thyrotrophic adenomas characteristically respond poorly to dopamine agonist treatment.
- Surgery is a common treatment for pituitary tumors. The normal approach is Trans-sphenoidal adenectomy, which usually can remove the tumor without affecting the brain or optic nerves.
- Danazol is a steroid compound that has been labelled as an "Anterior pituitary suppressant".
The first-line treatment of Cushing's disease is surgical resection of ACTH-secreting pituitary adenoma; this surgery involves removal of the tumor via transsphenoidal surgery (TSS).
There are two possible options for access to sphenoidal sinus including of endonosal approach (through the nostril) or sublabial approach (through an incision under the upper lip); many factors such as the size of nostril, the size of the lesion, and the preferences of the surgeon cause the selection of one access route over the other.
Some tumors do not contain a discrete border between tumor and pituitary gland; therefore, careful sectioning through pituitary gland may be required to identify the location of tumor. The probability of successful resection is higher in patients where the tumor was identified at initial surgery in comparison to patients where no tumor was found initially; the overall remission rates in patients with microadenomas undergoing TSS are in range of 65%-90%, and the remission rate in patients with macroadenomas are lower than 65%. patients with persistent disease after initial surgery are treated with repeated pituitary surgery as soon as the active persistent disease is evident; however, reoperation has lower success rate and increases the risk of pituitary insufficiency.
Pituitary radiation therapy is another option for treatment of postoperative persisting hypercortisolemia following unsuccessful transsphenoidal surgery. External-beam pituitary RT is more effective treatment for pediatric CD in children with cure rates of 80%-88%. Hypopituitarism specifically growth hormone deficiency has been reported as the only most common late morbidity of this treatment; GHD has been reported in 36% and 68% of the patients undergoing post pituitary RT for Cushing's disease.
Bilateral adrenalectomy is another treatment which provides immediate reduction of cortisol level and control of hypercortisolism. However, it requires education of patients, because lifelong glucocorticoid and mineralocorticoid replacement therapy is needed for these patients. One of the major complications of this treatment is progression of Nelson's syndrome which is caused by enhance level of tumor growth and ACTH secretion post adrenalectomy in 8%-29% of patients with CD.
During post surgical recovery, patients collect 24-hour urine sample and blood sample for detecting the level of cortisol with the purpose of cure test; level of cortisol near the detection limit assay, corresponds to cure. Hormonal replacement such as steroid is given to patients because of steroid withdrawal. After the completion of collecting urine and blood samples, patients are asked to switch to glucocorticoid such as prednisone to decrease symptoms associated with adrenal withdrawal.
A study of 3,525 cases of TSS for Cushing's disease in the nationally representative
sample of US hospitals between 1993 and 2002 was conducted and revealed the following results: the in-hospital mortality rate was 0.7%; the complication rate was 42.1%. Diabetes insipidus (15%), fluid and electrolyte abnormalities (12.5%), and neurological deficits (5.6%) were the most common complications reported. The analyses of the study show that complications were more likely in patients with pre-operative comorbidities. Patients older than 64 years were more likely to have an adverse outcome and prolonged hospital stay. Women were 0.3 times less likely to have adverse outcomes in comparison to men.
The deformities are managed surgically to preserve the function of the limb.
The goal of newborn screening programs is to detect and start treatment within the first 1–2 weeks of life. Treatment consists of a daily dose of thyroxine, available as a small tablet. The generic name is levothyroxine, and several brands are available. The tablet is crushed and given to the baby with a small amount of water or milk. The most commonly recommended dose range is 10-15 μg/kg daily, typically 12.5 to 37.5 or 44 μg.
Within a few weeks, the T and TSH levels are rechecked to confirm that they are being normalized by treatment. As the child grows up, these levels are checked regularly to maintain the right dose. The dose increases as the child grows.
Dubowitz syndrome is a rare genetic disorder characterized by microcephaly, stunted growth, and a receding chin. Symptoms vary among patients, but other characteristics include a soft, high-pitched voice; partial webbing of the fingers and toes; palate deformations; genital abnormalities; language difficulties; and an aversion to crowds. The pathogenesis of the disease is yet to be identified, and no medical tests can definitively diagnose the disease. The primary method of diagnosis is to identify facial phenotypes. Since it was first described in 1965 by English physician Victor Dubowitz, over 140 cases have been reported worldwide. Although the majority of cases have been reported from the United States, Germany, and Russia, the disorder appears to affect both genders and all ethnicities equally.
Microcephaly is a characteristic in which the circumference of the head is smaller than normal due to improper development of the brain. It is caused by genetic disorders, infections, radiation, medications or alcohol abuse during pregnancy. Defects in the growth of the cerebral cortex lead to many of the features associated with microcephaly. There is currently no known method of correcting microcephaly. However, there are a variety of symptomatic treatments that help to counter some of its adverse effects, such as speech and occupational therapies, as well as medication to control seizures and hyperactivity. Microcephaly has a vast range of prognoses: some patients experience little to very mental retardation and can reach regular age-appropriate milestones. Others may experience severe mental retardation and neuromuscular side effects.
Cushing's syndrome is a collection of signs and symptoms due to prolonged exposure to cortisol. Signs and symptoms may include high blood pressure, abdominal obesity but with thin arms and legs, reddish stretch marks, a round red face, a fat lump between the shoulders, weak muscles, weak bones, acne, and fragile skin that heals poorly. Women may have more hair and irregular menstruation. Occasionally there may be changes in mood, headaches, and a chronic feeling of tiredness.
Cushing's syndrome is caused by either excessive cortisol-like medication such as prednisone or a tumor that either produces or results in the production of excessive cortisol by the adrenal glands. Cases due to a pituitary adenoma are known as Cushing's disease. It is the second most common cause of Cushing's syndrome after medication. A number of other tumors may also cause Cushing's. Some of these are associated with inherited disorders such as multiple endocrine neoplasia type 1 and Carney complex. Diagnosis requires a number of steps. The first step is to check the medications a person takes. The second step is to measure levels of cortisol in the urine, saliva or in the blood after taking dexamethasone. If this test is abnormal, the cortisol may be measured late at night. If the cortisol remains high, a blood test for ACTH may be done to determine if the pituitary is involved.
Most cases can be treated and cured. If due to medications, these can often be slowly stopped. If caused by a tumor, it may be treated by a combination of surgery, chemotherapy, and/or radiation. If the pituitary was affected, other medications may be required to replace its lost function. With treatment, life expectancy is usually normal. Some, in whom surgery is unable to remove the entire tumor, have an increased risk of death.
About two to three people per million are affected each year. It most commonly affects people who are 20 to 50 years of age. Women are affected three times more often than men. A mild degree of overproduction of cortisol without obvious symptoms, however, is more common. Cushing's syndrome was first described by Harvey Cushing in 1932. Cushing's syndrome may also occur in other animals including cats, dogs, and horses.
Most children born with congenital hypothyroidism and correctly treated with thyroxine grow and develop normally in all respects. Even most of those with athyreosis and undetectable T levels at birth develop with normal intelligence, although as a population academic performance tends to be below that of siblings and mild learning problems occur in some.
Congenital hypothyroidism is the most common preventable cause of intellectual disability. Few treatments in the practice of medicine provide as large a benefit for as small an effort.
The developmental quotient (DQ, as per Gesell Developmental Schedules) of children with hypothyroidism at age 24 months that have received treatment within the first 3 weeks of birth is summarised below:
Vici syndrome, also called immunodeficiency with cleft lip/palate, cataract, hypopigmentation and absent corpus callosum, is a rare autosomal recessive congenital disorder characterized by albinism, agenesis of the corpus callosum, cataracts, cardiomyopathy, severe psychomotor retardation, seizures, immunodeficiency, and recurrent severe infections. To date about 50 cases have been reported.
Cushing's disease is a cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary (secondary hypercortisolism). This is most often as a result of a pituitary adenoma (specifically pituitary basophilism) or due to excess production of hypothalamus CRH (corticotropin releasing hormone) (tertiary hypercortisolism/hypercorticism) that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids.
This should not be confused with ectopic Cushing syndrome or exogenous steroid use.
Central diabetes insipidus, also called neurogenic diabetes insipidus, is a type of diabetes insipidus due to a lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion.
It is also known as neurohypophyseal diabetes insipidus, referring to the posterior pituitary (neurohypophysis), which is supplied by the hypothalamus in the brain. This condition has only polyuria in common with diabetes and although not mutually exclusive, with most typical cases, the name diabetes insipidus is a misleading misnomer. A better name might be "hypothalamic-neurohypophyseal ADH deficiency".
Hydrops-ectopic calcification-moth-eaten skeletal dysplasia is a defect in cholesterol biosynthesis. It is also known as Greenberg dysplasia. Greenberg characterized the condition in 1988.
It has been associated with the lamin B receptor.
Thyroid dysgenesis or thyroid agenesis is a cause of congenital hypothyroidism where the thyroid is missing, ectopic, or severely underdeveloped.
It should not be confused with iodine deficiency, or with other forms of congenital hypothyroidism, such as thyroid dyshormonogenesis, where the thyroid is present but not functioning correctly.
Congenital hypothyroidism caused by thyroid dysgenesis can be associated with PAX8.
No treatment is required, but neoplastic processes (metastatic maliganancy to the submandibular lymph nodes and/or salivary gland tumours) should be ruled out. This is usually done with clinical exam and imaging. Very rarely, since the defect contains salivary gland tissue, salivary gland tumors can occur within an established defect but there is likely no difference in the risk of neoplasia in salivary gland tissue at other sites.
Carcinomas that metastasize into the pituitary gland are uncommon and typically seen in the elderly, with lung and breast cancers being the most prevalent, In breast cancer patients, metastases to the pituitary gland occur in approximately 6-8% of cases.
Symptomatic pituitary metastases account for only 7% of reported cases. In those who are symptomatic Diabetes insipidus often occurs with rates approximately 29-71%. Other commonly reported symptoms include anterior pituitary dysfunction, visual field defects, headache/pain, and ophthalmoplegia.
Although generally benign, the cyst must be removed if the patient exhibits difficulty in breathing or swallowing, or if the cyst is infected. Even if these symptoms are not present, the cyst may be removed to eliminate the chance of infection or development of a carcinoma, or for cosmetic reasons if there is unsightly protrusion from the neck.
Thyroid scans and thyroid function studies are ordered preoperatively; this is important to demonstrate that normally functioning thyroid tissue is in its usual area.
Surgical management options include the Sistrunk procedure, en bloc central neck dissection, suture-guided transhyoid pharyngotomy, and Koempel's supra-hyoid technique. Cystectomy is an inadequate approach.
High phosphate levels can be avoided with phosphate binders and dietary restriction of phosphate. If the kidneys are operating normally, a saline diuresis can be induced to renally eliminate the excess phosphate. In extreme cases, the blood can be filtered in a process called hemodialysis, removing the excess phosphate.
The Sistrunk procedure is the surgical resection of the central portion of the hyoid bone along with a wide core of tissue from the midline area between the hyoid and foramen cecum. It involves excision not only of the cyst but also of the path's tract and branches, and removal of the central portion of the hyoid bone is indicated to ensure complete removal of the tract. The original Sistrunk papers (the "classic" procedure described in 1920, and the "modified" procedure described in 1928) are available on-line with a modern commentary.
In general, the procedure consists of three steps:
1. incision
2. resection of cyst and hyoid bone
3. drainage and closure
There are several versions of the Sistrunk procedure, including:
- "classic": excision of the center of the hyoid bone along with a thyroglossal duct cyst, removal of one-eighth inch diameter core of tongue muscle superior to the hyoid at a 45 degree angle up to the foramen cecum to include mucosa, removal of one-quarter inch of the center of the hyoid bone, closure of the cut ends of the hyoid bone, and placement of a drain.
- modified: dissection through the tongue base but not through the mucosa. The modified Sistrunk procedure is the procedure of choice in both primary and revision cases.
- hyoid cartilage division: In cases without mature ossification of the hyoid bone, the non-fused cartilage portion can be divided by monopolar Bovie electro-cauterization or scissors. There were no statistical differences between this modified Sistrunk and the conventional Sistrunk procedure.
The procedure is relatively safe. In a study of 35 pediatric patients, Maddalozzo et. al found no major complications, but did observe minor complications (6 patients presented with seroma and 4 patients with local wound infections). A more recent paper analyzed 24 research studies on different treatment complications of thyroglossal cyst, and reported a total minor complications rate of 6% for the Sistrunk operation (classical or modified) and simple cystectomy treatment modalities. The Sistrunk procedure also showed better outcomes concerning the rate of overall recurrence, i.e. has the lowest rate of recurrence.
Sistrunk procedure results in a 95% cure rate and 95–100% long-term survival.
An "ectopic thyroid", also called "accessory thyroid gland", is a form of thyroid dysgenesis in which an entire or parts of the thyroid located in another part of the body than what is the usual case. A completely ectopic thyroid gland may be located anywhere along the path of the descent of the thyroid during its embryological development, although it is most commonly located at the base of the tongue, just posterior to the foramen cecum of the tongue. In this location, an aberrant or ectopic thyroid gland is known as a "lingual thyroid". If the thyroid fails to descend to even higher degree, then the resulting final resting point of the thyroid gland may be high in the neck, such as just below the hyoid bone. Parts of ectopic thyroid tissue ("accessory thyroid tissue") can also occur, and arises from remnants of the thyroglossal duct, and may appear anywhere along its original length. Accessory thyroid tissue may be functional, but is generally insufficient for normal function if the main thyroid gland is entirely removed.
Lingual thyroid is 4-7 times more common in females, with symptoms developing during puberty, pregnancy or menopause. Lingual thyroid may be asymptomatic, or give symptoms such as dysphagia (difficulty swallowing), dysphonia (difficulty talking) and dyspnea (difficulty breathing).
Ectopic thymus is a condition where thymus tissue is found in an abnormal location.
It can be associated with failure of descent.
It can also be associated with failure of involution.
Clear diagnosis is useful to avoid unnecessary treatment and exclude more sinister diagnoses (for example, haemoptysis or pleural effusion could also indicate cancer). Overall treatment for pulmonary endometriosis is surgical, with subsegmentectomy. It is obviously important to preserve as much lung parenchyma as possible, while removing macroscopic signs of pathological tissue. Medical treatment includes gonadotropin-releasing hormone analogues, which can cause cessation of menstruation and decreased libido, as well as a 50% recurrence rate. Even in the asymptomatic, treatment is recommended to prevent possible complications listed above.
Stafne defect is uncommon, and has been reported to develop anywhere between the ages of 11 and 30 years old, (although the defect is developmental, it does not seem to be present form birth, implying that the lesion develops at a later age). Usually the defect is unilateral (on one side only) and most commonly occurs in men.