​Kembara Xtra - Medicine - Pituitary Adenoma

​Kembara Xtra - Medicine - Pituitary Adenoma 
Pituitary adenomas, which account for 10 to 25% of all brain tumors and are occasionally discovered by chance on magnetic resonance imaging (MRI), are typically benign, slow-growing tumors that develop from cells in the pituitary gland.
Prolactinoma (PRL) 25–40%, nonfunctioning pituitary adenomas 30%, somatotroph adenoma (growth hormone [GH]) 15-20%, corticotroph adenoma (adrenocorticotropic hormone [ACTH]) 5–10%, thyrotroph adenoma (thyroid-stimulating hormone [TSH]) 1%, and gonadotropinoma

Epidemiology 

 Predominant age: Incidence rises with age.
For microadenomas, females outnumber males (3:2) (men frequently experience a delayed diagnosis). Incidence
3-27% of patients with microadenomas and 0.5% of those with macroadenomas at autopsy had no pituitary problems.
In 1/10 people, MRI scans show anomalies consistent with pituitary adenoma.
18/100,000 people have pituitary tumors that are clinically evident.

Pathophysiology and Etiology 
Growth of monoclonal adenohypophysial cells Functional microadenomas' hormonal effects frequently lead to detection prior to mass effect.
 PRL enhanced by functioning prolactinomas or prevented stalk effect-induced dopaminergic inhibition. 
Genetics
Carney complex aryl hydrocarbon receptor-interacting protein gene (AIP) mutations account for 15% of familial solitary pituitary adenomas; they manifest earlier in life and are greater in size. Asthma McCune-Albright
MEN1 is short for multiple endocrine neoplasia. A germline mutation in the cyclindependent kinase inhibitor 1B (CDKN1B) causes the MEN1-like phenotype (MEN4). Approximately 40% of somatotroph adenomas have the activating mutation Gs-alpha (Gs), which affects the guanine nucleotide stimulatory protein (Gs) gene.

Risk Elements 

a variety of endocrine tumors

Common diagnosis
- Impotence, gynecomastia, amenorrhea, and galactorrhea are all symptoms of hyperprolactinemia. - Pain in the sellar region
- Biceps hemianopsia, a visual impairment
Less frequently, acromegaly (coarse facial features, hand/foot swelling, carpal tunnel syndrome, hyperhidrosis, left ventricular hypertrophy) is caused by hypersomatotropinemia. - Hyposomatotropinemia: asymptomatic in adults and failure to thrive (FTT) in youngsters - Increased intracranial pressure (ICP): headache, nauseousness, convulsions - Hypercorticotropinemia: Cushing illness (thickening of the supraclavicular and dorsocervical fat pads, moon face, hirsutism, acne, plethora, abdominal striae, centripetal obesity with thin limbs, easy bruising and bleeding, hyperglycemia) - Apoplexy: headache, abrupt collapse
Palpitations, diaphoresis, heat intolerance, and diarrhea are symptoms of secondary hyperthyroidism. Weakness, irritability, anorexia, and nausea/vomiting are symptoms of secondary adrenal insufficiency.  Hypothalamic compression: abnormalities of body temperature, thirst, and appetite

clinical assessment 
Common: Bitemporal hemianopsia; Visual abnormalities; Hyperprolactinemia; Hypogonadism; Galactorrhea; Gynecomastia
- Acromegaly (coarse features, swollen hands and feet, and diaphoresis) caused by hypersomatotropinemia - FTT (kids) hyposomatotropinemia
ICP rise is less frequent with dementia and papilledema.
Cushing disease symptoms include centripetal obesity, thickening of the supraclavicular fat pad, the moon face, hirsutism, and acne. Apoplexy symptoms include hypotension, hypoglycemia, tachycardia, and oliguria.
Tachycardia, tachypnea, diaphoresis, warm/moist skin, and tremor are symptoms of secondary hyperthyroidism. - Orthostatic hypotension during an adrenal crisis
Hypothalamic compression: abnormal regulation of body temperature, obesity, and excessive urine 

Multiple Diagnoses 

Pituitary hyperplasia, Rathke cleft cyst, granulomatous illness, such as tuberculosis, lymphocytic hypophysitis, metastatic tumor, germinoma, and craniopharyngioma are a few conditions that can cause this condition. 

Laboratory Results 

Based on suspected dysfunctions, choose
Somatotrophic (GH production ranges from 40 to 130/million) - Acromegaly/hypersomatotropinemia: increased serum levels of IGF-1; oral glucose tolerance test with GH administered at 0, 30, and 60 minutes (usually suppresses GH to 1 g/L) - Macimorelin is a non-invasive oral test to assess for adult GH deficit. - Hyposomatotropinemia: low GH-releasing hormone response.
Corticotropic - hypercorticotropinemia/Cushing illness
- Overnight lowdose dexamethasone suppression test (DMST): normal free plasma cortisol (FPC) >1.8 g/dL at 8 AM (after 1 mg given at 11 PM the night before) - 24-hour urinary-free cortisol >50 g - ACTH level assay: 20 pg/mL = adrenal tumor; 20 pg/mL = ectopic/pituitary source (if DMST findings are abnormal) - High-dose corticotropin stimulation test for hypocorticotropinemia/secondary glucocorticoid deficiency: FPC 10 g/dL at baseline, increasing by 25% 1 hour after 250 g; metyrapone test: 11-deoxycortisol 150 ng/L after 2 g provided (Be ready to administer steroids as a test may exacerbate insufficiency.) Thyrotrophic (TSH secreting): hyper-/hypothyroidism: TSH and free T4 both increased for pituitary hyperthyroidism and both decreased for pituitary hypothyroidism. Gonadotrophic/hypogonadotropism: gonadotropin-releasing hormone stimulation of LH/FSH blunted in pituitary hypergonadism but increased in primary hypogonadism.

Initial examinations (lab, imaging)
PRL, GH, IGF-1, ACTH, 24-hour urine-free cortisol or overnight DMST, - HCG, FSH, LH, TSH, and free T4 make up a common panel for asymptomatic tumors.
Maintain the same levels of GH and IGF-1 through patient treatment. Where accessible, families of patients with pituitary adenoma may be offered screening for AIP mutations.
After biochemical confirmation, MRI is recommended (>90% sensitivity and specificity). Octreotide scintigraphy is helpful in identifying tumors with somatostatin receptors.
Diagnostic Techniques/Other Inferior Petrosal Sinus Sampling: To differentiate between ectopic ACTH and Cushing illness (a pituitary source), ACTH was taken from the inferior petrosal sinuses.
Immunohistochemistry was used to identify specific cell types. Under a light microscope, eosinophilic (GH, PRL), basophilic (FSH/LH, TSH, ACTH), and chromophobic cells were observed.
Prolactinomas respond best to medical treatment, which is also an adjuvant treatment for other tumors.
First Line: MEDICATION
Dopamine agonists augment the PRL dopaminergic suppression in hyperprolactinemia.
- Cabergoline, a D2 receptor-specific drug (Dostinex).
Initial dose: 0.25 mg PO once or twice per week; maintenance dose: 0.25 mg PO twice per week per PRL (maximum 2 mg/week), increased every four weeks.
Ergot sensitivity, uncontrolled hypertension (HTN), and pregnancy are contraindications. Precautions include liver impairment.
Tricyclic antidepressants, phenothiazines, and opiates may all inhibit it.  Adverse effects include hot flushes, vertigo, dyspepsia, and orthostatic hypotension. - Bromocriptine, a D2 receptor-specific drug (Parlodel).
Initial dose: 1.25 to 2.50 mg PO daily (give with food); maintenance dose: 2.5 mg/day increased every two to seven days; maximum daily dose: 15 mg.
Ergot sensitivity, uncontrolled high blood pressure, and pregnancy are contraindications; if necessary, cabergoline is preferable.
Tricyclic antidepressants, phenothiazines, and opiates may all inhibit it.  Adverse effects include myocardial infarction, stroke, convulsions, and orthostatic hypotension. Somatotropinoma - Long-acting analogues of somatostatin (Sandostatin LAR and lanreotide Autogel); titrate in accordance with package insert; contraindication: hypersensitivity; precautions: use with biliary, thyroid, cardiac, liver, or kidney disease. More effective as an adjuvant than a primary treatment for somatotropinomas; consider using somatostatin analogue or pegvisomant in patients with severe residual disease; consider using cabergoline in patients with mild residual disease.
Pegvisomant (Somavert) is a GH receptor antagonist. The recommended starting dose is 40 mg SC 1 followed by 10 mg daily, with titrations of 5 mg every 4 to 6 weeks based on IGF-1 values. The maximum daily maintenance dose is 30 mg. Hypersensitivity is a contraindication.
 Caution: use with extreme caution if you have diabetes, liver disease, or tumors that secrete growth hormone. NSAIDs, opiates, insulin, and oral glycemic medications interact with each other.
Hepatitis, tumor growth, and GH secretion are side effects. Corticotropinemia is treated with peripheral inhibitors such as Mitotane (Lysodren). The initial dose is 2 to 6 g/day divided PO TID (max 19 g/day). The maintenance dose is 2 to 16 g TID. Hypersensitivity is a contraindication.
Adverse reactions include HTN, orthostatic hypotension, hemorrhagic cystitis, and dermatitis. Interactions include contraindication with the rotavirus vaccine and caution with other vaccines. - Ketoconazole Dosing: 200 mg PO TID (max 1,200 mg/day) Contraindications: hypersensitivity, achlorhydria, fungal meningitis, impaired liver function Precautions: use caution if you have liver disease Interactions: not recommended with dronedarone, methadone, statins, pimozide, or sirolimus; use caution with other antifungals Adrenal insufficiency, thrombocytopenia, hepatic failure, hepatotoxicity, anaphylaxis, leukopenia, and hemolytic anemia are some of the negative side effects. Pasireotide (Signifor): No contraindications; dosage: initially 0.6 to 0.9 mg twice daily, subsequently 0.3 to 0.9 mg twice daily
Hypocortisolism, hyperglycemia, bradycardia or QT prolongation, elevated liver tests, cholelithiasis, and other pituitary hormone deficits are precautions. - Korlym (mifepristone)
Dosage: Give one PO dose with a meal each day. The suggested beginning dose is 300 mg once daily; renal impairment requires a maximum daily dose of 600 mg. Pregnancy, the use of simvastatin or lovastatin and CYP3A substrates with a narrow therapeutic range, concurrent long-term corticosteroid use, women with a history of unexplained vaginal bleeding, and women with endometrial hyperplasia with atypia or endometrial carcinoma are contraindications. Precautions include adrenal insufficiency, hypokalemia, vaginal bleeding and endometri
Drug use should be stopped or nursing should end for nursing mothers.
- Adverse reactions: In people with Cushing syndrome, the following are the most frequent (20%): HTN, dizziness, decreased appetite, nausea, fatigue, headache, low blood potassium, arthralgia, vomiting, peripheral edema, and endometrial enlargement  Bromocriptine for gonadotropinemia.
Somatostatin analogues and thyrotropinemia Observe the preceding debate.

Peripheral inhibitors in the second line for corticotropinemia include metyrapone.
250 mg PO QID is the dosage.
Porphyria is a contraindication.
 Caution in cases of liver or thyroid disorders
Dilantin raises metabolism, which is an interaction.
 Negative effects include nausea and hypotension
 Octreotide-related gonadotropinemia: Observe the preceding debate.


Referral Ophthalmologist examination prior to surgery Neurosurgery consultation for symptomatic tumors (apart from prolactinoma) 

Supplemental Therapies 

Stereotactic radiosurgery can be used as an alternative to surgery in high-risk patients or as an addition when fractionated radiation is insufficient. 

Surgery The majority of surgeries are now performed endoscopically using a translabial/transsphenoidal route.
 Follow-up: serial neurologic/hormonal examinations to assess consequences (such as diabetes insipidus, CNS injury), as well as the need for additional therapy. Remission rates: 72-87% for microadenomas, but only 50-56% for macroadenomas.

Admission 

Unless there is an adrenal or apoplexic crisis, outpatient management
Pituitary apoplexy must be treated right away to avoid death.
In individuals who are weak or hemodynamically unstable, stress-dose steroids may be an option.
 Maintain blood pressure with fluids and/or pressors.
If polyuria or electrolytes are out of balance, check the sodium, osmolality, and specific gravity of your blood and urine.
 Speak with neurosurgery.
Hyperosmolar IV fluids for diabetes insipidus Adrenal crisis: saline solution Pituitary apoplexy: Perform frequent neurologic examinations and monitor inputs/outputs (I/Os), central venous pressure, and ICP.
Watch the BP and I/Os during an adrenal crisis.
Continue to be treated as an inpatient following surgery until diabetes insipidus and/or adrenal insufficiency are controlled.


Patient Follow-Up Monitoring
The involved hormone(s) are monitored postoperatively, particularly after radiation because hypopituitarism may appear 10 to 15 years after treatment. Follow-up MRIs are performed at 6 and 12 months after discharge.

Prognosis is based on the kind, size, symptoms, and treatment.

Complications include: postoperative diabetes insipidus and/or hypogonadism (usually temporary/common); pituitary apoplexy (acute/uncommon); acute hemorrhagic pituitary infarction; adrenal crisis with severe headache; and the need for surgical decompression to prevent shock, coma, and death; Nelson syndrome (subacute/uncommon): rapid adenoma growth postadrenalectomy; pitu

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