Exam I DPT V (Lapointe)

Drugs Stimulation of Prolactin

Phenothiazines (chlorpromazine)

Haloperidol

Methyldopa

Opioids

Estrogen

MAO Inhibitor (Phenelzine)

Drug Inhibition of Prolactin

"dopamine agonists": levodopa, bromocriptine, cabergoline

What drug stimulates LH and FSH?

Clomiphene (estrogen receptor modulator- ovulation modulator)

What drugs can inhibit ACTH?

dopamine agonists and somatostatin analogs

What drugs can inhibit LH and FSH?

estrogen, testosterone, gonadotropin-releasing hormone (leuprolide)

What is the gold standard for diagnosing acromegaly?

oral glucose tolerance test

Why is the oral glucose tolerance test gold standard for acromegaly?

GH would fail the test rather than oral glucose is normal

since GH is considered to be anti-insulin

Nonfunctioning tumors

not responsive to medications and require surgery and/or irradiation

What are the treatment of choice for prolactinomas?

dopamine agonists

Dopamine Agonists

Bromocriptine

Cabergoline

Bromocriptine

dopamine agonist (for MILD cases)

> 50% improve mild-mod symptoms of acromegaly

Cabergoline

improve moderate symptoms of acromegaly

more potent, will bring down IGF-1 and GH

tumor size can shrink when taking this

What are the most common side effects of dopamine agonist?

GI: abdominal pain, diarrhea (take with food), nausea

CNS: dizziness, headache, lightheadedness, nervousness, fatigue

psychiatric disturbances, addiction

Somatostatin Analogs

primary therapy in patients who cannot be cured by surgery or poor surgical candidates

Octreotide (Sandostatin)

long acting IM formulation

could be used for severe diarrhea, IBS, carcinoid tumors, variceal bleeding

can improve symptoms FOR SURE, normalization of GH and IGF-1, MORE POTENT than dopamine agonists

Lanreotide

more potent and safer side effect profile than octreotide

Pasireotide

may result in greater GH inhibition

For Octreotide or Lanreotide-resistant adenomas!!

Common side effects of somatostatin analogs

GI

injection site pain

biliary tract disorders

Which somatostatin analog has less injection site pain and biliary tract disorders and abnormalities in glucose metabolism?

lanreotide

Adverse effects of Pasireotide

higher incidence of hyperglycemia

often require TX with antidiabetes medications

Monitoring for somatostatin analogs

GH and IGF-1 3monthers after

Monitoring for PEGvisomant

liver function tests monthly for 6 months

IGF-1 after first year

Monitoring for Dopamine Agonist

GH, IGF-1, and prolactin concentration 4-6 weeks after

Does PEGvisomant decrease growth hormone?

NO!

What is first line for acromegaly?

somatostatin like drugs

When should you add cabergoline to acromegaly treatment?

you can add to SRL if IGF1 remains modestly elevated or to relieve mild symptoms

If IGF-1 is positive and 10x normal, what could this indication?

acromegaly

What are the two star medications in hyperprolactinoma?

cabergoline and bromocriptine

When can bromocriptine be first line for hyperprolactinoma?

mild symptoms, cost less

Panhypopituitarism

complete or partial loss of anterior and posterior pituitary function

multiple pituitary hormone deficiencies

Hormone replacement for ACTH

hydrocortisone

cortisone acetate

prednisone

Hormone replacement for TSH

L-Thyroxine

Hormone replacement for FSH/LH

testosterone

estrogen, progesterone, estradiol

Hormone replacement for GH

Somatotropin

Hormone replacement for Vasopressin

desmopressin

Clinical Presentation of Cushing Syndrome

facial rounding

hump on upper back

bone fractures

muscle weakness

central weight gain

What drugs can given you Cushing Syndrome?

long term use of corticosteroid

medroxyprogesterone, megestrol acetate

prescription glucocorticoid preparations (most routes)

Hydrocortisone Replacement Dose

20 mg

Prednisone/Prednisolone Replacement Dose

5 mg

Methylprednisone/Methylprednisolone Replacement Dose

4 mg

Dexamethasone Replacement Dose

0.75 mg

What two progestins have been associated with developing Cushing's Syndrome?

medroxyprogesterone acetate

megestrol acetate

Tests for Cushing Syndrome

24 hours urinary free cortisol

overnight dexamethasone suppression test

late-night salivary cortisol (elevated night salivary)

What drugs target cortisol production?

ketoconazole, metyrapone, etomidate, mitotane

What drug can decrease tumor ACTH production?

Cabergoline, Pasireotide

Glucocorticoid Receptor Antagonist

Mifepristone

Etomidate

can give you adrenal insuffiency on the spot

HP access suppression, bring blood pressure down

Traditional Approach to Cushing Syndrome

Ketoconazole 200 mg TID, titrate to 400 mg TID, add Metyrapone 250 mg TID

Increase Metyrapone to 4 g/day

Consider Mitotane

When should you NOT use ketoconazole?

warfarin

digoxin

rifampin

Clinical Presentation of Addison's Disease

hypotension

hyperpigmentation

hyponatremia

hyperkalemia

anorexia and weight loss

fatigue and malaise

HPA axis suppression

normotension or hypotension

weight loss

hypoglycemia

hyponatremia

eukalemia

What are the drug-induced adrenal insufficiency?

chronic glucocorticoid administration

steroidogenesis inhibitors

megestrol acetate

mifepristone

tyrosine kinase inhibitors

inducers of cyp p450 enzymes that increase cortisol metabolism

Diagnosis of AI

corticotropin (cosyntropin) stimulation test

Cosyntropin Stim Test

administration of ACTH (cosyntropin)

check morning and check cortisol level 30-60 minutes later

post: < 18

post vs pre change in < 9

Dexamethasone

cause something to shrink

will not give you that sodium and water retention

Mineralocorticoid Supplementation

fludrocortisone 0.05-0.2 mg daily

Fludrocortisone

no anti-inflammatory properties

salt and water retention

may seen for Addison's disease or orthostatic hypertension

Clinical Presentation of Hypoaldosteronism

weight loss

gastrointestinal disturbances

dizziness, lightheadedness

salt-craving

severe postural HYPOtension

HYPOnatremia

HYPERkalemia

HYPERchloremia metabolic acidosis

How do you treat hypoaldosteronism?

fludrocortisone 0.1-0.3 mg daily

Clinical Presentation of Aldosteronism

hypertension

muscle tetany

excessive thirst

increase ARR

excessive urination

hypernatremia

glucose intolerance

hypomagnesemia

hypokalemia

How to treat bilateral adrenal hyperplasia aldosteronism?

spironolactone, eplerenone, and amiloride

How to treat glucocorticoid remediable aldosteronism?

low-dose glucocorticoids: dexamethasone 0.5 mg daily or Prednisone 2.5-5 mg daily

All of the following regarding hyperprolactinemia are true except

A. a medication that increase dopamine can induce hyperprolactinemia

B. females with hyperprolactinemia may experience oligomenorrhea or amenorrhea

C. If medical therapy is warranted, treatment with cabergoline is an option

D. use of antipsychotics can cause hyperprolactinemia

A

A 20 year old woman is being evaluated for GH deficiency. The newer macimorelin test is used, and her GH concentration is 1.6. Which supplemental test would be least useful for this patient?

A. Lipid panel

B. Depression screening

C. Skin biopsy

D. Echocardiogram

C

A 36-year-old kidney transplant patient recently started octreotide LAR for acromegaly. Her current medications include lisinopril 5 mg PO daily, insulin glargine 25 units daily, cyclosporine 25 mg PO daily, prednisone 60 mg PO daily, and sulfamethoxazole/trimethoprim 800/160 mg PO twice daily. Which of the following medication(s) will likely require dosage adjustment in this patient?

A. Cyclosporine

B. Insulin glargine

Which one of the following medications requires monitoring of liver function tests?

A. Cabergoline

B. Octreotide

C. Lanreotide

D. Pegvisomant

D

Which one of the following GH-deficient patients may require a lower initial GH replacement dose of 0.1 to 0.2 mg/day?

A. Prepubertal child

B. Teenager during puberty

C. Adult who has an underweight BMI

D. Adult with diabetes

D

Which one of the following pituitary gland disorder and clinical presentation pair combinations is correct?

A. Acromegaly: infertility

B. GH deficiency: depression

C. Hyperprolactinemia: enlarged hands

D. Hyperprolactinemia: hypergonadism

B

A 28-year-old woman presents to the pharmacist-run clinic for her annual wellness visit. She has been taking lanreotide SR for acromegaly and still has residual GH-secreting tumor. She plans on trying to conceive next year after getting married. What would be the most appropriate recommendation about her lanreotide SR therapy?

A. Substitute lanreotide SR with pegvisomant 2 months prior to conception

B. Substitute lanreotide SR with pasireotide 2 months prior to conception

C. Substitute lanreotide SR with octreotide LAR 2 months prior to conception

D. Substitute lanreotide SR with short-acting octreotide 2 months prior to conception

D

All of the following complications are associated with prolonged exposure of elevated growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations in patients with acromegaly, except:

A. Colon cancer

B. Osteoarthritis

C. Diabetes Mellitus

D. Urinary incontinence

D

All of the following are important to evaluate when a patient presents with elevated prolactin concentration of 30 mcg/mL (mcg/L), except:

A. Use dopamine antagonist medications

B. Use of beta blocker medications

C. Presence of chronic renal failure

D. Presence of hypothyroidism

B

A 58-year-old woman with uncontrolled type 2 diabetes mellitus and hypertension was recently diagnosed with acromegaly. With her macroadenoma extending to the optic chiasm, patient is not a surgical candidate. Her recent HgbA1c is 10.9% (0.109; 96 mmol/mol Hb). What is the most appropriate treatment to initiate for the patient at this time?

A. Pasireotide

B. Lanreotide

C. Pegvisomant

D. Cabergoline

B

A 35-year-old woman has been taking cabergoline for hyperprolactinemia, which has helped her achieve regular ovulatory cycles. She is now pregnant and asks you if she can continue cabergoline during pregnancy. What is the most appropriate recommendation regarding management of hyperprolactinemia during pregnancy?

A. Discontinue cabergoline; resume in third trimester

B. Continue cabergoline until third semester; then discontinue

C. Switch to bromocriptine for reaming duration of pregnancy

D. Discontinue cabergoline for remaining duration of pregnancy

D

A 52-year-old man with acromegaly underwent transsphenoidal pituitary surgery for his microadenoma 6 months ago but continues to require pharmacotherapy with lanreotide Autogel 120 mg every 4 weeks. After 4 months of treatment on lanreotide, the patient exhibits partial response to therapy. What is the most appropriate treatment regimen for the patient at this time?

A. Continue lanreotide, start pegvisomant

B. Discontinue lanreotide, start pegvisomant

C. Continue lanreotide, increase frequency of injections

D. Discontinue lanreotide, initiate radiation therapy

A

A 30-year-old woman presents with infrequent menstruation, headache, and weight gain. Diagnosis of hyperprolactinemia is confirmed with elevated prolactin concentration of 70 ng/mL (mcg/L). Over the last year, the patient has been closely monitored as she has been trying to conceive without any success. Which one of the following treatment options is the most appropriate for the patient at this time?

A. Bromocriptine 0.625 mg at bedtime without birth control

B. Cabergoline 0.25 mg twice weekly with adequate birth control

C. Refer for transsphenoidal microsurgery

D. Refer for radiation therapy

B

A 35-year-old patient with normal BMI has been diagnosed with growth hormone deficiency. She has no other comorbidities. What is the most appropriate titration schedule for her GH hormone replacement therapy based on clinical response, serum IGF-I concentrations, and side effects?

A. 0.05-0.1 mg/day at 1-2 month intervals

B. 0.1-0.2 mg/day at 1-2 month intervals

C. 0.2-0.3 mg/day at 2-3 month intervals

D. 0.3-0.4 mg/day at 2-3 month intervals

B

All of the following statements regarding the oral somatostatin analog octreotide (Mycapssa) are true, except:

A. The starting dose for patients with end-stage renal disease is lower than the usual starting dose.

B. It is first oral somatostatin analog approved and available on the market.

C. It is available as a delayed-release rather than immediate-release formulation

D. It is more effective compared to long-acting injectable somatostatin analog

D

What two hormones does the hypothalamus synthesize?

oxytocin and vasopressin (ADH)

What organ is responsible for the synthesis and release of hormones that regulate the pituitary gland?

hypothalamus

High concentrations of what can inhibit GH secretion through somatostatin thereby inhibiting GHRH secretion at hypothalamus?

IGF-1

Which hormone has the anti-insulin effect?

growth hormone

Acromegaly

rare disorder that manifests gradually over time and typically occurs after fusion of the epiphyses of the long bones

Signs and Symptoms of Acromegaly

large hand and facial features

elevation in IGF-1

What is the measurement that is needed to diagnose acromegaly?

IGF-1 and oral glucose tolerance test

lack of suppression of GH after oral glucose > 1

Gigantism

GH excess that occurs during childhood

What is the first line agent for Acromegaly?

somatostatin receptor ligands

If the patient is a partial responder to the SRL, what should you do next?

increase dose and/or dose frequency

If the patient has optimized SRL and still have IGF-1 modestly elevated, what should you add next?

Cabergoline

If acromegaly has not been controlled after SRL + cabergoline, what should you do?

switch to pasireotide IF clinically relevant

Patients with impaired glucose tolerance should be switched to what drug if SRL and cabergoline does not work?

pegvisomant

Patients with impaired glucose tolerance and tumor concern should be treatment with a combination of what in acromegaly?

first-gen SRL and pegvisomant

Which drug for acromegaly can cause hyperglycemia?

pasireotide

Which drug for acromegaly can cause abnormal liver enzymes and sweating?

pegvisomant

Due to somatostatin analogs inhibiting the gallbladder contractility and bile secretion, what may result as an adverse effect?

gallstones and biliary sludge

What drugs may require dosage adjustment due to potential adverse effects or bioavailability?

insulin, cyclosporine, beta blockers, CCB, or oral hypoglycemic agents

Which dopamine agonist is preferred due to its improved tolerability and extended duration of action?

cabergoline

Approximately 2 months prior to conception, what should LAF of somatostatin analogs and pegvisomant be substituted with?

short acting octreotide

What test is considered gold standard for GH deficiency?

insulin tolerance test however more so now is glucagon stimulation test

What is the main pharmacologic treatment for GH deficiency in both children and adults?

recombinant GH therapy

When should a patient administer their GH injection?

evening