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Several hormone deficiencies associated with hypopituitarism may lead to secondary diseases. For instance, growth hormone deficiency is associated with obesity, raised cholesterol and the metabolic syndrome, and estradiol deficiency may lead to osteoporosis. While effective treatment of the underlying hormone deficiencies may improve these risks, it is often necessary to treat them directly.
Dopamine is the chemical that normally inhibits prolactin secretion, so doctors may treat prolactinoma with bromocriptine, cabergoline or Quinagolide drugs that act like dopamine. This type of drug is called a dopamine agonist. These drugs shrink the tumor and return prolactin levels to normal in approximately 80% of patients. Both have been approved by the Food and Drug Administration for the treatment of hyperprolactinemia. Bromocriptine is associated with side-effects such as nausea and dizziness and hypotension in patients with already low blood pressure readings. To avoid these side-effects, it is important for bromocriptine treatment to start slowly.
Bromocriptine treatment should not be interrupted without consulting a qualified endocrinologist. Prolactin levels often rise again in most people when the drug is discontinued. In some, however, prolactin levels remain normal, so the doctor may suggest reducing or discontinuing treatment every two years on a trial basis. Recent studies have shown increased success in remission of prolactin levels after discontinuation, in patients having been treated for at least 2 years prior to cessation of bromocriptine treatment.
Cabergoline is also associated with side-effects such as nausea and dizziness, but these may be less common and less severe than with bromocriptine. However, people with low blood pressure should use caution when starting cabergoline treatment, as the long half-life of the drug (4–7 days) may inadvertently affect their ability to keep their blood pressure within normal limits, creating intense discomfort, dizziness, and even fainting upon standing and walking until the single first dose clears from their system. As with bromocriptine therapy, side-effects may be avoided or minimized if treatment is started slowly. If a patient's prolactin level remains normal for 6 months, a doctor may consider stopping treatment. Cabergoline should not be interrupted without consulting a qualified endocrinologist.
The goal of treatment is to return prolactin secretion to normal, reduce tumor size, correct any visual abnormalities, and restore normal pituitary function. As mentioned above, the impact of stress should be ruled out before the diagnosis of prolactinoma is given. Exercise can significantly reduce stress and, thereby, prolactin levels. In the case of very large tumors, only partial reduction of the prolactin levels may be possible.
Pituitary tumors require treatment when they are causing specific symptoms, such as headaches, visual field defects or excessive hormone secretion. Transsphenoidal surgery (removal of the tumor by an operation through the nose and the sphenoidal sinuses) may, apart from addressing symptoms related to the tumor, also improve pituitary function, although the gland is sometimes damaged further as a result of the surgery. When the tumor is removed by craniotomy (opening the skull), recovery is less likely–but sometimes this is the only suitable way to approach the tumor. After surgery, it may take some time for hormone levels to change significantly. Retesting the pituitary hormone levels is therefore performed 2 to 3 months later.
Prolactinomas may respond to dopamine agonist treatment–medication that mimics the action of dopamine on the lactrotrope cells, usually bromocriptine or cabergoline. This approach may improve pituitary hormone secretion in more than half the cases, and make supplementary treatment unnecessary.
Other specific underlying causes are treated as normally. For example, hemochromatosis is treated by venesection, the regular removal of a fixed amount of blood. Eventually, this decreases the iron levels in the body and improves the function of the organs in which iron has accumulated.
Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births. More than 1000 individuals have been identified with thyroid hormone resistance, of which 85% had thyroid hormone beta receptor mutation.
Beta blockers, like Atenolol, are sometimes used to help suppress symptoms.
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".
There is no known cure for acromegaly. The goals of treatment are to reduce GH production to normal levels, to relieve the pressure that the growing pituitary tumor exerts on the surrounding brain areas, to preserve normal pituitary function, and to reverse or ameliorate the symptoms of acromegaly. Currently, treatment options include surgical removal of the tumor, drug therapy, and radiation therapy of the pituitary.
The primary current medical treatment of acromegaly is to use somatostatin analogues – octreotide (Sandostatin) or lanreotide (Somatuline).
These somatostatin analogues are synthetic forms of a brain hormone, somatostatin, which stops GH production. The long-acting forms of these drugs must be injected every 2 to 4 weeks for effective treatment. Most patients with acromegaly respond to this medication. In many patients, GH levels fall within one hour and headaches improve within minutes after the injection. Octreotide and lanreotide are effective for long-term treatment. Octreotide and lanreotide have also been used successfully to treat patients with acromegaly caused by non-pituitary tumors.
Somatostatin analogues are also sometimes used to shrink large tumors before surgery.
Because octreotide inhibits gastrointestinal and pancreatic function, long-term use causes digestive problems such as loose stools, nausea, and gas in one third of patients. In addition, approximately 25 percent of patients develop gallstones, which are usually asymptomatic. In some cases, octreotide treatment can cause diabetes due to the fact that somatostatin and its analogues can inhibit the release of insulin.
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.
For more information on the form in horses, see pituitary pars intermedia dysfunction.
In endocrinology, medical emergencies include diabetic ketoacidosis, hyperosmolar hyperglycemic state, hypoglycemic coma, acute adrenocortical insufficiency, phaeochromocytoma crisis, hypercalcemic crisis, thyroid storm, myxoedema coma and pituitary apoplexy.
Emergencies arising from decompensated pheochromocytomas or parathyroid adenomas are sometimes referred for emergency resection when aggressive medical therapies fail to control the patient's state, however the surgical risks are significant, especially blood pressure lability and the possibility of cardiovascular collapse after resection (due to a brutal drop in respectively catecholamines and calcium, which must be compensated with gradual normalization). It remains debated when emergency surgery is appropriate as opposed to urgent or elective surgery after continued attempts to stabilize the patient, notably in view of newer and more efficient medications and protocols.
Direct treatment is geared toward resolving hyperprolactinemic symptoms or reducing tumor size. Patients on medications that cause hyperprolactinaemia should have them withdrawn if possible. Patients with hypothyroidism should be given thyroid hormone replacement therapy. When symptoms are present, medical therapy is the treatment of choice. Patients with hyperprolactinemia and no symptoms (idiopathic or microprolactinoma) can be monitored without treatment. Consider treatment for women with amenorrhea. In addition, dual energy X-ray absorptiometry scanning should be considered to evaluate bone density. The persistent hypogonadism associated with hyperprolactinemia can lead to osteoporosis. Treatment significantly improves the patient's quality of life. If the goal is to treat hypogonadism only, patients with idiopathic hyperprolactinemia or microadenoma can be treated with estrogen replacement therapy and prolactin levels can be monitored. Radiation treatment is another option. However, the risk of hypopituitarism makes this a poor choice. It may be necessary for rapidly growing tumors, but its benefits in routine treatment have not been shown to outweigh the risks.
General indications for pituitary surgery include patient drug intolerance, tumors resistant to medical therapy, patients who have persistent visual field defects in spite of medical treatment, and patients with large cystic or hemorrhagic tumors.
Treatment for Addison's disease involves replacing the missing cortisol, sometimes in the form of hydrocortisone tablets, or prednisone tablets in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively, one-quarter as much prednisolone may be used for equal glucocorticoid effect as hydrocortisone. Treatment is usually lifelong. In addition, many patients require fludrocortisone as replacement for the missing aldosterone.
People with Addison's are often advised to carry information on them (e.g., in the form of a MedicAlert bracelet or information card) for the attention of emergency medical services personnel who might need to attend to their needs. It is also recommended that a needle, syringe, and injectable form of cortisol be carried for emergencies. People with Addison's disease are advised to increase their medication during periods of illness or when undergoing surgery or dental treatment. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A patient who is vomiting may require injections of hydrocortisone instead.
Standard therapy involves intravenous injections of glucocorticoids and large volumes of intravenous saline solution with dextrose (glucose). This treatment usually brings rapid improvement. If intravenous access is not immediately available, intramuscular injection of glucocorticoids can be used. When the patient can take fluids and medications by mouth, the amount of glucocorticoids is decreased until a maintenance dose is reached. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.
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.
Most patients with thyroid adenoma can be managed by watchful waiting (without surgical excision) with regular monitoring. However, some patients still choose surgery after being fully informed of the risks. Regular monitoring mainly consists of watching for changes in nodule size and symptoms, and repeat ultrasonography or needle aspiration biopsy if the nodule grows.
Treatment of HH may consist of administration of either a GnRH agonist or a gonadotropin formulation in the case of primary HH and treatment of the root cause (e.g., a tumor) of the symptoms in the case of secondary HH. Alternatively, hormone replacement therapy with androgens and estrogens in males and females, respectively, may be employed.
A pituitary disease is a disorder primarily affecting the pituitary gland.
The main disorders involving the pituitary gland are:
Overproduction or underproduction of a pituitary hormone will affect the respective end-organ. For example, insufficient production (hyposecretion) of thyroid stimulating hormone (TSH) in the pituitary gland will cause hypothyroidism, while overproduction (hypersecretion) of TSH will cause hyperthyroidism. Thyroidisms caused by the pituitary gland are less common though, accounting for less than 10% of all hypothyroidism cases and much less than 1% of hyperthyroidism cases.
Treatment may consist of surgery in the case of tumors, lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males.
Toxic multinodular goiter can be treated with antithyroid medications such as propylthiouracil or methimazole, radioactive iodine, or with surgery.
Another treatment option is injection of ethanol into the nodules.
Growth hormone-releasing hormone (GHRH) is another releasing factor secreted by the hypothalamus. GHRH stimulates the pituitary gland to secrete growth hormone (GH), which has various effects on body growth and sexual development. Insufficient GH production may cause poor somatic growth, precocious puberty or gonadotropin deficiency, failure to initiate or complete puberty, and is often associated with rapid weight gain, low T, and low levels of sex hormones.
In larger case series, the mortality was 1.6% overall. In the group of patients who were unwell enough to require surgery, the mortality was 1.9%, with no deaths in those who could be treated conservatively.
After an episode of pituitary apoplexy, 80% of people develop hypopituitarism and require some form of hormone replacement therapy. The most common problem is growth hormone deficiency, which is often left untreated but may cause decreased muscle mass and strength, obesity and fatigue. 60–80% require hydrocortisone replacement (either permanently or when unwell), 50–60% need thyroid hormone replacement, and 60–80% of men require testosterone supplements. Finally, 10–25% develop diabetes insipidus, the inability to retain fluid in the kidneys due to a lack of the pituitary antidiuretic hormone. This may be treated with the drug desmopressin, which can be applied as a nose spray or taken by mouth.
Treatment is usually medication with dopamine agonists such as cabergoline, bromocriptine (often preferred when pregnancy is possible), and less frequently lisuride. A new drug in use is norprolac with the active ingredient quinagolide. Terguride is also used.
"Vitex agnus-castus" extract can be tried in cases of mild hyperprolactinaemia.