Neuroendócrino Flashcards
Como tratar o hipopituitarismo?
(1) Hormone replacement therapy, including glucocorticoids, thyroid hormone, sex steroids, growth hormone, and vasopressin, is usually safe and free of complications.
A.Hydrocortisone (10–20 mg A.M.; 5–10 mg P.M.) / Prednisone (5 mg A.M.)
B. L-Thyroxine (0.075–0.15 mg daily
C. Testosterone skin patch (5 mg/d) / Conjugated estrogen (0.65–1.25 mg qd for 25 days) Progesterone (5–10 mg qd) on days 16–25
D. Somatotropin (0.1–1.25 mg SC qd)
E. Intranasal desmopressin (5–20 μg twice daily) Oral 300–600 μg qd
(2) Patients in need of glucocorticoid replacement require careful dose adjustments during stressful events such as acute illness, dental procedures, trauma, and acute hospitalization.
Qual a avaliação de massas selares e supraselares?
(1) Sagittal and coronal T1-weighted MRI imaging before and after administration of gadolinium allows precise visualization of the pituitary gland with clear delineation of the hypothalamus, pituitary stalk, pituitary tissue and surrounding suprasellar cisterns, cavernous sinuses, sphenoid sinus, and optic chiasm
(2) Because optic tracts may be contiguous to an expanding pituitary mass, reproducible visual field assessment using perimetry techniques should be performed on all patients with sellar mass lesions that abut the optic chiasm
(3) nitial hormonal evaluation usually includes (1) basal PRL; (2) insulin-like growth factor (IGF) I; (3) 24-h urinary free cortisol (UFC) and/or overnight oral dexamethasone (1 mg) suppression test; (4) α subunit, FSH, and LH; and (5) thyroid function tests. Additional hormonal evaluation may be indicated based on the results of these tests. Pending more detailed assessment of hypopituitarism, a menstrual history, measurement of testosterone and 8 A.M. cortisol levels, and thyroid function tests usually identify patients with pituitary hormone deficiencies that require hormone replacement before further testing or surgery
Quais as opções terapêuticas para tumores selares e supraselares?
(1) Transsphenoidal rather than transfrontal resection is the desired surgical approach for pituitary tumors, except for the rare invasive suprasellar mass surrounding the frontal or middle fossa or the optic nerves or invading posteriorly behind the clivus. Intraoperative microscopy facilitates visual distinction between adenomatous and normal pituitary tissue as well as microdissection of small tumors that may not be visible by MRI. mor size, the degree of invasiveness, and experience of the surgeon largely determine the incidence of surgical complications. Operative mortality rate is about 1%. Transient diabetes insipidus and hypopituitarism occur in up to 20% of patients. Permanent diabetes insipidus, cranial nerve damage, nasal septal perforation, or visual disturbances may be encountered in up to 10% of patients. CSF leaks occur in 4% of patients.
(2) Radiation is used either as a primary therapy for pituitary or parasellar masses or, more commonly, as an adjunct to surgery or medical therapy. Focused megavoltage irradiation is achieved by precise MRI localization, using a high-voltage linear accelerator and accurate isocentric rotational arcing. A major determinant of accurate irradiation is reproduction of the patient’s head position during multiple visits and maintenance of absolute head immobility. A total of <50 Gy (5000 rad) is given as 180-cGy (180-rad) fractions divided over about 6 weeks. Stereotactic radiosurgery delivers a large single high-energy dose from a cobalt 60 source (gamma knife), linear accelerator, or cyclotron. Longterm effects of gamma-knife surgery are unclear but appear to be similar to those encountered with conventional radiation. Alopecia and loss of taste and smell may be more long-lasting. Failure of pituitary hormone synthesis is common in patients who have undergone head and neck or pituitary-directed irradiation. More than 50% of patients develop loss of GH, ACTH, TSH, and/or gonadotropin secretion within 10 years, usually due to hypothalamic damage. Optic nerve damage with impaired vision due to optic neuritis is reported in about 2% of patients. The cumulative risk of developing a secondary tumor after conventional radiation is 1.3% after 10 years and 1.9% after 20 years
(3) Medical therapy for pituitary tumors is highly specific and depends on tumor type. For prolactinomas, dopamine agonists are the treatment of choice. For acromegaly, somatostatin analogues and GH receptor antagonists are indicated. For TSH-secreting tumors, somatostatin analogues and occasionally dopamine agonists are indicated. ACTH-secreting tumors and nonfunctioning tumors are generally not responsive to medications and require surgery and/or irradiation
Qual o manejo da hiperprolactinemia?
(1) If the patient is taking a medication known to cause hyperprolactinemia, the drug should be withdrawn, if possible. For psychiatric patients who require neuroleptic agents, supervised dose titration or the addition of a dopamine agonist can help restore normoprolactinemia and alleviate reproductive symptoms. However, dopamine agonists sometimes worsen the underlying psychiatric condition, especially at high doses.
(2) Hyperprolactinemia usually resolves after adequate thyroid hormone replacement in hypothyroid patients or after renal transplantation in patients undergoing dialysis.
(3) Resection of hypothalamic or sellar mass lesions can reverse hyperprolactinemia caused by stalk compression and reduced dopamine tone.
(4) Granulomatous infiltrates occasionally respond to glucocorticoid administration.
(5) In patients with irreversible hypothalamic damage, no treatment may be warranted. In up to 30% of patients with hyperprolactinemia—usually without a visible pituitary microadenoma—the condition may resolve spontaneously
Quais os objetivos do tratamento do prolactinoma e como fazer o seguimento?
(1) For symptomatic microadenomas, therapeutic goals include control of hyperprolactinemia, reduction of tumor size, restoration of menses and fertility, and resolution of galactorrhea. Dopamine agonist doses should be titrated to achieve maximal PRL suppression and restoration of reproductive function. These patients should be monitored by regular serial PRL and MRI measurements
(2) For macroadenomas, formal visual field testing should be performed before initiating dopamine agonists. MRI and visual fields should be assessed at 6- to 12-month intervals until the mass shrinks and annually thereafter until maximum size reduction has occurred
Quais as drogas utilizadas para tratar o prolactinoma?
(1) Cabergoline (0.5 to 1.0 mg twice weekly) achieves normoprolactinemia and resumption of normal gonadal function in ∼80% of patients with microadenomas; galactorrhea improves or resolves in 90% of patients. Cabergoline normalizes PRL and shrinks ∼70% of macroprolactinomas. Mass effect symptoms, including headaches and visual disorders, usually improve dramatically within days after cabergoline initiation; improvement of sexual function requires several weeks of treatment but may occur before complete normalization of prolactin levels. After initial control of PRL levels has been achieved, cabergoline should be reduced to the lowest effective maintenance dose. In ∼5% of treated patients harboring a microadenoma, hyperprolactinemia may resolve and not recur when dopamine agonists are discontinued after long-term treatment
(2) In microadenomas bromocriptine rapidly lowers serum prolactin levels to normal in up to 70% of patients, decreases tumor size, and restores gonadal function. In patients with macroadenomas, prolactin levels are also normalized in 70% of patients and tumor mass shrinkage (≥50%) is achieved in most patients. Therapy is initiated by administering a low bromocriptine dose (0.625–1.25 mg) at bedtime with a snack, followed by gradually increasing the dose. Most patients are controlled with a daily dose of ≤7.5 mg (2.5 mg tid).
Side effects of dopamine agonists include constipation, nasal stuffiness, dry mouth, nightmares, insomnia, and vertigo; decreasing the dose usually alleviates these problems. Nausea, vomiting, and postural hypotension with faintness may occur in ∼25% of patients after the initial dose. These symptoms may persist in some patients. In general, fewer side effects are reported with cabergoline. For the approximately 15% of patients who are intolerant of oral bromocriptine, cabergoline may be better tolerated.
When pregnancy is confirmed, bromocriptine should be discontinued and PRL levels followed serially, especially if headaches or visual symptoms occur. For women harboring macroadenomas, regular visual field testing is recommended, and the drug should be reinstituted if tumor growth is apparent. Although pituitary MRI may be safe during pregnancy, this procedure should be reserved for symptomatic patients with severe headache and/or visual field defects. Surgical decompression may be indicated if vision is threatened. Although comprehensive data support the efficacy and relative safety of bromocriptinefacilitated fertility, patients should be advised of potential unknown deleterious effects and the risk of tumor growth during pregnancy
Qual o tratamento cirúrgico do prolactinoma?
Indications for surgical adenoma debulking include dopamine resistance or intolerance and the presence of an invasive macroadenoma with compromised vision that fails to improve after drug treatment. Initial PRL normalization is achieved in about 70% of microprolactinomas after surgical resection, but only 30% of macroadenomas can be resected successfully. Follow-up studies have shown that hyperprolactinemia recurs in up to 20% of patients within the first year after surgery; long-term recurrence rates exceed 50% for macroadenomas. Radiotherapy for prolactinomas is reserved for patients with aggressive tumors that do not respond to maximally tolerated dopamine agonists and/or surgery.
Quais são as opções terapêuticas da acromegalia?
In summary, surgery is the preferred primary treatment for GH-secreting microadenomas. The high frequency of GH hypersecretion after macroadenoma resection usually necessitates adjuvant or primary medical therapy for these larger tumors. Patients unable to receive or respond to unimodal medical treatment may benefit from combined treatments or can be offered radiation.
(1) Transsphenoidal surgical resection by an experienced surgeon is the preferred primary treatment for both microadenomas (cure rate ∼70%) and macroadenomas (<50% cured). Soft tissue swelling improves immediately after tumor resection. In ∼10% of patients, acromegaly may recur several years after apparently successful surgery; hypopituitarism develops in up to 15% of patients after surgery.
(2) Octreotide is administered by subcutaneous injection, beginning with 50 μg tid; the dose can be increased gradually up to 1500 μg/d. Fewer than 10% of patients do not respond to the analogue. Octreotide suppresses integrated GH levels and normalizes IGF-I levels in ∼75% of treated patients. The long-acting somatostatin depot formulations, octreotide and lanreotide, are the preferred medical treatment for patients with acromegaly. SandostatinLAR is a sustained-release, long-acting formulation of octreotide incorporated into microspheres that sustain drug levels for several weeks after intramuscular injection. GH suppression occurs for as long as 6 weeks after a 30-mg intramuscular injection; long-term monthly treatment sustains GH and IGF-I suppression and also reduces pituitary tumor size in ∼50% of patients. Somatostatin analogues are well tolerated in most patients. Adverse effects are short-lived and mostly relate to drug-induced suppression of gastrointestinal motility and secretion. Nausea, abdominal discomfort, fat malabsorption, diarrhea, and flatulence occur in one-third of patients, and these symptoms usually remit within 2 weeks. (Somatostatin analogue)
(3) Pegvisomant is administered by daily subcutaneous injection (10–20 mg) and normalizes IGF-I in >90% of patients. GH levels, however, remain elevated as the drug does not have antitumor actions. Side effects include reversible liver enzyme elevation, lipodystrophy, and injection site pain. Tumor size should be monitored by MRI. Combined treatment with monthly somatostatin analogues and weekly or biweekly pegvisomant injections has been used effectively in resistant patients. (GH receptor antagonist)
(4) Bromocriptine and cabergoline may modestly suppress GH secretion in some patients. High doses of bromocriptine (≥20 mg/d) or cabergoline (0.5 mg/d) are usually required to achieve modest GH therapeutic efficacy. Combined treatment with octreotide and cabergoline may induce additive biochemical control compared with either drug alone.
(5) An advantage of radiation is that patient compliance with long-term treatment is not required. Patients may require interim medical therapy for several years before attaining maximal radiation benefits. Most patients also experience hypothalamicpituitary damage, leading to gonadotropin, ACTH, and/ or TSH deficiency within 10 years of therapy.
(6) Systemic sequelae of acromegaly, including cardiovascular disease, diabetes, and arthritis, should be managed aggressively. Mandibular surgical repair may be indicated
Qual o tratamento da doença de Cushing?
(1) Selective transsphenoidal resection is the treatment of choice for Cushing’s disease. The remission rate for this procedure is ∼80% for microadenomas but <50% for macroadenomas.
(2) When initial surgery is unsuccessful, repeat surgery is sometimes indicated, particularly when a pituitary source for ACTH is well documented. Pituitary irradiation may be used after unsuccessful surgery, but it cures only about 15% of patients.
(3) Ketoconazole, an imidazole derivative antimycotic agent, inhibits several P450 enzymes and effectively lowers cortisol in most patients with Cushing’s disease when administered twice daily (600–1200 mg/d). Elevated hepatic transaminases, gynecomastia, impotence, gastrointestinal upset, and edema are common side effects. Mitotane (o,p′DDD; 3–6 g/d orally in four divided doses) suppresses cortisol hypersecretion by inhibiting 11β-hydroxylase and cholesterol side-chain cleavage enzymes and by destroying adrenocortical cells. Side effects of mitotane include gastrointestinal symptoms, dizziness, gynecomastia, hyperlipidemia, skin rash, and hepatic enzyme elevation. It also may lead to hypoaldosteronism. Other agents include aminoglutethimide (250 mg tid), trilostane (200–1000 mg/d), cyproheptadine (24 mg/d), and IV etomidate (0.3 mg/kg per hour).
(4) The use of steroidogenic inhibitors has decreased the need for bilateral adrenalectomy. Removal of both adrenal glands corrects hypercortisolism but may be associated with significant morbidity rates and necessitates permanent glucocorticoid and mineralocorticoid replacement. Adrenalectomy in the setting of residual corticotrope adenoma tissue predisposes to the development of Nelson’s syndrome, a disorder characterized by rapid pituitary tumor enlargement and increased pigmentation secondary to high ACTH levels. Radiation therapy may be indicated to prevent the development of Nelson’s syndrome after adrenalectomy.
Como tratar adenomas produtores de TSH?
The initial therapeutic approach is to remove or debulk the tumor mass surgically, usually using a transsphenoidal approach. Total resection is not often achieved as most of these adenomas are large and locally invasive. Normal circulating thyroid hormone levels are achieved in about two-thirds of patients after surgery. Thyroid ablation or antithyroid drugs (methimazole and propylthiouracil) can be used to reduce thyroid hormone levels. Somatostatin analogue treatment effectively normalizes TSH and α subunit hypersecretion, shrinks the tumor mass in 50% of patients, and improves visual fields in 75% of patients; euthyroidism is restored in most patients. Because somatostatin analogues markedly suppress TSH, biochemical hypothyroidism often requires concomitant thyroid hormone replacement, which may also further control tumor growth
Quais os seis hormônios produzidos pela hipófise anterior?
The anterior pituitary gland produces six major hormones: (1) prolactin (PRL), (2) growth hormone (GH), (3) adrenocorticotropic hormone (ACTH), (4) luteinizing hormone (LH), (5) folliclestimulating hormone (FSH), and (6) thyroid-stimulating hormone (TSH)
Quais os dois objetivos na síndrome de Cushing?
The diagnosis of Cushing’s syndrome presents two great challenges: (1) to distinguish patients with pathologic cortisol excess from those with physiologic or other disturbances of cortisol production and (2) to determine the etiology of cortisol excess.
