pituitary disorders

what is acromegaly

•Condition of excessive production of growth hormone (GH)

•Most common cause is a pituitary adenoma (tumor)

Leads to soft tissue growth

what can acromegaly lead to

Can lead to multiple issues

• Cardiovascular disease

• Joint issues

• Elevated glucose for some patients

acromegaly treatment

• Most cases can be treated with surgery

• In some cases, medications may be needed instead of or as adjuncts to surgery

acromegaly treatment goal

• Treatment goal is to reduce GH and insulin-like growth factor (IGF-1)

  • IGF-1 is a key mediator of IGF-1

  • GH level goal below 1 mcg/L or lower depending on test sensitivity

  • IGF-1 goal is to be normal for age and gender

  • Can measure these following oral glucose tolerance test (OGTT)

    • See if therapy is effective (measure elevated glucose)

  • GH should drop when glucose is elevated

chart for acromegaly management

dopamine agonist drugs

Cabergoline or Bromocriptine

dopamine agonist

• Dopamine normally stimulates release of growth hormone (GH)

• Dopamine agonists (DAs) can have a paradoxical decrease of GH in acromegaly

• Likely related to abnormal expression of dopamine 2 (D2) receptor on pituitary tumors

• Different DAs than used for Parkinson’s

  • For GH, Das are ergot derivatives

  • DA for Parkinson’s are non-ergot and have differences in dopamine receptor binding

  • bromocriptine used less frequently

  • cabergoline used primarily due to greater efficacy over bromocriptine

• DAs are least expensive options and have oral administration but less effective than others

dopamine agonist adverse reaction

• Gastrointestinal effects

  • Nausea common

  • Remember: these do the opposite of dopamine antagonists that help with nausea

  • Taking with food may help

• CNS effects

  • Dizziness

  • Impulse control: important to warn patients

• Cardiovascular

  • Orthostatic drop

  • Peripheral edema: may be overlooked as a med cause

  • Potential for valvular heart disease with cabergoline

somatostatin analogs

•Mimic natural somatostatin

•Natural somatostatin inhibits growth hormone release

•Also decreases insulin release and affect multiple mediators in digestive tract

•octreotide and lanreotide considered similar efficacy

•pasireotide has affinity for more somatostatin receptor subtypes and may treat adenomas resistant to the other somatostatin analogs

somatostatin drugs

• octreotide SUBQ: given 3 times daily

• octreotide depot:

  • IM every 28 days

  • can use if benefit on SUBQ for at least 2 weeks

• octreotide oral: twice daily

  • Indicated if has tolerated octreotide SUBQ or lanreotide

  • Very expensive and potentially not covered by insurance

• lanreotide (Somatuline® depot): deep SUBQ every 28 days

• pasireotide (Signifor®): monthly intramuscular injection

somatostatin analog considerations

• Lower doses recommended for renal and hepatic impairment

• Potential gastrointestinal effects, including gallstones

• Glucose effect may vary

  • may be impacted by both medication and degree of acromegaly

  • pasireotide may cause more hyperglycemia

  • glucose monitoring important

• Monitor for benefit and side effects and dose adjustment as needed

  • GH, IGF-1

  • Longer acting require multiple doses to evaluate

what to monitor for somatostatin

• glucose

• GH, IGF-1

pegvisomant (Somavert) MOA

• Growth Hormone Receptor Antagonist

  • Blocks effect of growth hormone rather than affecting release

  • Most effective mechanism

pegvisomant (Somavert) monitor

•Daily subcutaneous injection

•More expensive than somatostatin analog injections

•GH will not decrease but monitor IGF-1

pegvisomant (Somavert) side effects

• gastrointestinal effects and flu-like symptoms

• elevation of hepatic aminotransferase, requiring liver function monitoring

acromegaly points

• combination treatment with medications of different classes may be needed if insufficienty response to monotherapy

• greater risk for adverse effects

growth hormone deficiency

• May happen in children but not necessarily continue into adulthood

• Growth Hormone may be used in adults who have a confirmed growth hormone deficiency

• Growth hormone treatment not generally recommended in older adults

  • Beers Criteria indicates risk generally outweighs benefit

  • Exception is replacement for pituitary gland removal

growth hormone products

• Multiple products are available

• One not considered more effective than the other

  • 2 products requiring once weekly dosing are available

  • others require daily injection

growth hormone product contraindication

history of malignancy

what to monitor for growth hormone product

may increase blood glucose, so glucose monitoring is required

growth hormone products rare effects

pseudotumor cerebri (idiopathic intracranial hypertension)

• Headache, visual issues

• Usually develops in first 8 to 12 weeks

• Requires discontinuation

IGF-1 deficiency

•Some children may have primary deficiency of IGF-1

•Alternatively, may have IGF-1 deficiency with a resistance to GH

IGF-1 deficiency treatment

Treatment is mecasermin (Increlex®) given by subcutaneous injection

• recombinant IGF-1

• can cause hypoglycemia

• needs to be administered within 20 minutes of eating food to avoid hypoglycemia

• not indicated for adults

mecasermin (Increlex) counseling

• can cause hypoglycemia

• administer within 20 min of eating food to avoid hypoglycemia

monitoring growth hormone deficiency

•Needs consistent monitoring to adjust doses

•Monitor height, weight growth and IGF-1 levels

•Dose adjustments needed as a child grows

•Glucose and thyroid monitoring important

•Measure bone age every 6 to 12 months

•For adults, continue to monitor IGF-1

hyperprolactinemia

• Prolactin increases normally during pregnancy

• Any other elevations abnormal

  • Premenopausal women have naturally higher levels than men and postmenopausal women

• In women can cause menstrual irregularities

• In both men and women can affect sex steroid synthesis and affect libido

• Can cause galactorrhea in both men and women and gynecomastia in men

hyperprolactinemia cause

Primary causes are pituitary adenomas

• More often affects women; primarily have microadenomas

• Men more likely to have macroadenomas

medication that can cause hyperprolactinemia

• dopamine antagonists most direct effect

• dopamine has an inhibitory effect on prolactin release

• SSRIs, SNRIs, TCAs

• estrogen, progesterone

• variety of other medications have been associated

hyperprolactinemia treatment

•Surgery may be indicated for some patients

•Pharmacologic: dopamine agonists

• Cabergoline primary treatment

hyperprolactinemia primary treatment

•Cabergoline primary treatment

•Considered more effective and fewer side effects than bromocriptine

•Can actually shrink tumors over time

dopamine agonist monitoring for hyperprolactinemia treatment

•Monitoring every 6 to 12 months

•Can consider dose reduction or withdrawing treatment with improvement over time

•If a woman becomes pregnant, dopamine agonists not recommended during pregnancy (monitoring therapy) unless the adenoma becomes more severe

Syndrome of Inappropriate Anti-Diuretic Hormone

issue with not being able to suppress AVP

AVP responsibility and what it causes

AVP responsible for helping with retention of water

• Results in fluid retention

• Concentrates urine

• Causes hyponatremia from dilution and urine loss

SIADH causes

• different potential causes

• tumors secreting AVP

• CNS issues: (ex: stroke, trauma)

• medications

medications that cause SIADH

• chlorpropamide

• carbamazepine/oxcarbazepine

• SSRIs

• various others

SIADH treatment

• Treat underlying condition

  • If possible

  • Key for pharmacists is to help determine if medication can be the cause

• Fluid restriction (<1L/day)

  • may be difficult to maintain

  • may not be appropriate for all situations depending on underlying issue(s)

• Salt (sodium) supplements: depending on sodium level/severity

• Diuresis: generally mild diuresis used

AVP receptor antagonist drug

•Tolvaptan (Samsca®): also called “vasopression antagonist”

AVP receptor antagonist when to use

•Reserved if other treatments not effective

tolvaptan concerns

Concern about overcorrection/correction too rapidly

• Careful monitoring required and only recommended in hospital

• Fluid restriction during initiation not recommended to avoid overcorrection

tolvaptan duration of treatment

not recommended beyond 30 days

tolvaptan warning

has a warning about liver harm (specifically for high dose to treat polycystic kidney disease)

other medications for SIADH

•Some data with SGLT-2 inhibitors

•Urea has been given but limited evidence

•Demeclocycline: nephrotoxicity concerns

•Lithuim: not common

arginine vasopressin deficiency (AVP-D) causes

•posterior pituitary being unable to produce AVP (neurogenic)

•kidneys do not respond well to AVP (nephrogenic)

what does AVP-D result in

•Polyuria

•Nocturia

•Increase in serum sodium and osmolality: from concentration due to water loss

•Polydipsia (increased thirst): response to increase water intake to balance

AVP-D primary treatment

For neurogenic, primary treatment is desmopressin (DDAVP®)

• analog of AVP

• replacing the key hormone

desmopressin dosage forms

•Oral tablet for those who can swallow

•Nasal spray

additional AVP-D treatment

• May be helped by low sodium, lower protein diet (decreased solute diet)

• Low-dose hydrochlorothiazide may help, especially for nephrogenic

• NSAIDs, especially indomethacin have been used-for fluid retention

• Others have been utilized but not common because of some AVP effects

  • chlorpropamide

  • carbamazepine

  • clofibrate

AVP-D monitoring

• Sodium levels

• Urine output

• Continued need based on underlying issue

  • May be permanently needed for some patients

  • Others may improve with improvement in underlying condition