Endocrine and Metabolic Disorders PDF

Endocrine and Metabolic Disorders I. THYROID DISORDERS Hypothalamus TRH -ve Pituitary TSH -ve Thyroid T3 T4 Figure 1. Hypothalamus-pituitary-thyroid axis. a T4 is converted to T3 by peripheral tissue. Only unbound (free) thyroid hormone is biologically active. T3 = triiodothyronine; T4 = th...

Endocrine and Metabolic Disorders I. THYROID DISORDERS Hypothalamus TRH -ve Pituitary TSH -ve Thyroid T3 T4 Figure 1. Hypothalamus-pituitary-thyroid axis. a T4 is converted to T3 by peripheral tissue. Only unbound (free) thyroid hormone is biologically active. T3 = triiodothyronine; T4 = thyroxine; TRH = thyrotropin-releasing hormone; TSH = thyroid-stimulating hormone; -ve = negative feedback loop. Patient Case 1. A 43-year-old non-pregnant woman has received a diagnosis of Graves disease. She is reluctant to try ablative therapy and wants to try oral pharmacotherapy first. Her thyroid laboratory values today include TSH 0.22 mIU/L (normal 0.5–4.5 mIU/L) and free T4 3.2 ng/dL (normal 0.8–1.9 ng/dL). She is anxious and always feels warm when others say it is too cold. Which is best for initial treatment of her condition? A. Lugol’s solution. B. Propylthiouracil. C. Atenolol. D. Methimazole. A. Hyperthyroid Disorders (thyrotoxicosis) 1. Classification a. Toxic diffuse goiter (Graves disease): Most common hyperthyroid disorder i. Autoimmune disorder ii. Thyroid-stimulating antibodies directed at thyrotropin receptors mimic TSH and stimulate triiodothyronine (T3) and thyroxine (T4) production. b. Pituitary adenomas: Produce excessive TSH secretion that does not respond to normal T3 negative feedback c. Toxic adenoma: Nodule in thyroid, autonomous of pituitary, and TSH d. Toxic multinodular goiter (Plummer disease): Several autonomous follicles that, if large enough, cause excessive thyroid hormone secretion ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-204 Endocrine and Metabolic Disorders e. Painful subacute thyroiditis: Self-limiting inflammation of the thyroid gland caused by viral invasion of the parenchyma, resulting in the release of stored hormone f. Drug induced (e.g., excessive exogenous thyroid hormone dosages, amiodarone therapy) 2. Diagnosis a. Elevated free T4 serum concentrations b. Suppressed TSH concentrations (except in TSH-secreting adenomas) c. If examination and history do not provide the exact etiology, radioactive iodine uptake can be used. i. Radioactive iodine uptake elevated if thyroid gland is actively and excessively secreting T4 and/or T3: Graves disease, TSH-secreting adenoma, toxic adenoma, multinodular goiter ii.  Radioactive iodine uptake is suppressed in disorders caused by thyroiditis or hormone ingestion. d. Can also assess for the presence of various thyroid-related antibodies (thyroid stimulating, thyrotropin receptor, or thyroperoxidase), thyroglobulin, and thyroid biopsy 3. Clinical presentation a. Weight loss or increased appetite b. Lid lag c. Heat intolerance d. Goiter e. Fine hair f. Heart palpitations or tachycardia g. Nervousness, anxiety, insomnia h. Menstrual disturbances (lighter or more infrequent menstruation, amenorrhea) caused by hypermetabolism of estrogen i. Sweating or warm, moist skin j. Exophthalmos, also known as opthalmopathy or thyroid eye disease 4. Therapy goals a. Minimize or eliminate symptoms, improve quality of life b. Minimize long-term damage to organs (heart disease, arrhythmias, sudden cardiac death, bone demineralization, and fractures) c. Normalize free T4 and TSH concentrations 5. Therapeutics a. Ablative therapy: Common treatment for Graves disease, toxic nodule, multinodular goiter; radioactive iodine ablative therapy and surgical resection for adenomas according to patient preferences or comorbidities. Ablative therapy often results in hypothyroidism. b. Thyroidectomy c. Antithyroid pharmacotherapy can be used for: i. Those awaiting ablative therapy or surgical resection (a) Depletes stored hormone (b) Minimizes risk of posttreatment hyperthyroidism caused by thyroiditis ii. Those who are not ablative or surgical candidates (e.g., serious cardiovascular disease, candidate unlikely to be adherent to radiation safety) iii. When ablative therapy or surgical resection fails to normalize thyroid function iv. Those with a high probability of remission with oral therapy for Graves disease (a) Mild disease (b) Small goiter (c) Low or negative antibody titers (d) Women v. Those with limited life expectancy vi. Those with moderate to severe active Graves ophthalmopathy ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-205 Endocrine and Metabolic Disorders d. Thioureas (i.e., propylthiouracil, methimazole) i. Mechanism of action: Inhibits iodination and synthesis of thyroid hormones; propylthiouracil can block T4/T3 conversion in the periphery as well at high doses ii. Dosing (a) Propylthiouracil (1) Initial: 50–150 mg by mouth three times daily (2) Once euthyroid, can reduce to 50 mg two or three times daily (3) Recommended over methimazole in the first trimester of pregnancy because of the risk of embryopathy; can change to methimazole in second trimester (b) Methimazole (1) Preferred agent for Graves disease according to the American Association of Clinical Endocrinologists (AACE) and the American Thyroid Association for most patients (2) Initial: 10–30 mg by mouth once daily (use higher dose in those with higher baseline free T4 concentrations) (3) Once euthyroid, may reduce to 5–10 mg/day (c) Monthly dosage titrations as needed (depending on symptoms and free T4 concentrations); (1) TSH may remain low for months after therapy begins (2) Early in therapy, total T3 may be a better marker of efficacy than free T4. iii. Adverse effects (a) Hepatotoxicity risk (boxed warning for propylthiouracil): Consider baseline liver function tests. Routine evaluation of liver function while receiving antithyroid agents has not been shown to prevent severe hepatotoxicity. (b) Rash (c) Arthralgia, lupus-like symptoms (d) Fever (e) Agranulocytosis early in therapy (usually within 3 months): Guidelines recommend a baseline complete blood cell count; no routine monitoring recommended. Can repeat if patient becomes febrile or develops pharyngitis (f) Acute pancreatitis with methimazole iv. Efficacy (a) Slow onset in reducing symptoms (weeks). Maximal effect may take 4–6 months. (b) Neither drug appears superior to the other in efficacy. (c) On a milligram-to-milligram basis, methimazole is 10-fold more potent than propylthiouracil. (d) Remission rates low: 20%–30%. Remission is defined as normal TSH and T4 for 1 year after discontinuing antithyroid therapy. (e) Therapy duration in Graves disease (oral agents unlikely to cause remission in those with nodular thyroid disease) (1) Usually 12–18 months; length of trial might not affect remission rate (2) Consider trial off oral therapy if TSH is normal; antibody titers can help guide decision. (3) Monitor thyroid concentrations every 1–3 months for up to 12 months for relapse (abnormal TSH or T4 return). e. Nonselective β-blockers (primarily propranolol; sometimes nadolol) i. Mechanism of action: Blocks many hyperthyroidism manifestations mediated by β-adrenergic receptors; also may block (less active) T4 conversion to (more active) T3 when used at high doses ii. Propranolol dosing (a) Initial: 20–40 mg by mouth three or four times daily (b) Maximal: 240–480 mg/day ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-206 Endocrine and Metabolic Disorders iii. iv. Adverse effects (see Hypertension section in Chronic Care in Cardiology chapter) Efficacy (a) Used primarily for symptomatic relief (e.g., palpitations, tachycardia, tremor, anxiety) (b) Guidelines recommend use in all symptomatic patients, especially older adults and others with heart rates greater than 90 beats/minute or existing cardiovascular disease. Also recommended for use before ablative iodine therapy in those who are extremely symptomatic or have a free T4 2–3 times the upper limit of normal (c) Poor remission rates: 20%–35% (d) Alternatives to β-blockers: Clonidine, non-dihydropyridine calcium channel blocker f. Iodines and iodides (e.g., Lugol’s solution, saturated solution of potassium iodide) i. Mechanism of action: Inhibits the release of stored thyroid hormone. Minimal effect on hormone synthesis. Helps decrease vascularity and size of gland before surgery ii. Dosing (a) Lugol’s solution (6.3–8 mg of iodide per drop) (b) Saturated solution of potassium iodide (38–50 mg of iodide per drop) (c) Potassium iodide tablets: 130 mg tablets contain 100 mg of iodide. (d) Usual daily dose: 120–400 mg mixed with juice or water, split three times daily iii. Adverse effects (a) Hypersensitivity (b) Metallic taste (c) Soreness or burning in mouth or tongue (d) Do not use in the days before ablative iodine therapy (may reduce uptake of radioactive iodine). iv. Efficacy (a) Limited efficacy after 7–14 days of therapy because thyroid hormone release will resume (b) Primary use is temporary before surgery (7–10 days) to shrink the gland. (c) Can be used after ablative therapy (3–7 days) to inhibit thyroiditis-mediated release of stored hormone (d) Used acutely in thyroid storm g. Treatment of thyroid eye disease i. Teprotumumab: Insulin-like growth factor-1 (IGF-1) receptor inhibiting monoclonal antibody ii. Shown to reduce proptosis (eye protrusion) iii. Administered by intravenous injection B. Subclinical Hyperthyroidism 1. Definition: Low (below lower limit of reference range) or undetectable TSH with normal T4 2. Risk a. Associated with elevated risk of atrial fibrillation in patients older than 60 b. Associated with elevated risk of bone fracture in postmenopausal women c. Conflicting data about mortality risk 3. Treatment similar to treatment of overt hyperthyroidism a. Oral antithyroid drug therapy alternative to ablative therapy in young patients with Graves disease b. β-Blockers may help control cardiovascular morbidity, especially with atrial fibrillation. 4. If untreated, screen regularly for the development of overt hyperthyroidism (elevated free T4 concentrations). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-207 Endocrine and Metabolic Disorders C. Thyroid Storm 1. Severe and life-threatening decompensated thyrotoxicosis. Mortality rate may be as high as 20%. 2. Precipitating causes: Trauma, infection, antithyroid agent withdrawal, severe thyroiditis, postablative therapy (especially if inadequate pretreatment) 3. Presentation: Fever, tachycardia, vomiting, dehydration, coma, tachypnea, delirium 4. Pharmacotherapy a. Propylthiouracil i. 500- to 1000-mg loading dose; then 250 mg every 4 hours ii. Blocks new hormone synthesis iii. Can use methimazole 60–80 mg daily b. Iodide therapy 1 hour after propylthiouracil initiation (dosed as stated earlier) to block hormone release c. β-Blocker therapy: Propranolol or esmolol commonly used to control symptoms and block conversion of T4 to T3 in high doses d. Acetaminophen as antipyretic therapy, if needed (avoid nonsteroidal anti-inflammatory drugs because of displacement of protein-bound thyroid hormones) e. Corticosteroid therapy: Hydrocortisone 300-mg intravenous loading dose; then 100 mg every 8 hours (or equivalent dosages of, for example, dexamethasone, prednisolone). Provides prophylaxis against relative adrenal insufficiency and can block conversion of T4 to T3 Patient Case 2. A 63-year-old woman has Hashimoto disease. Her thyroid laboratory values today include TSH 10.6 mIU/L (normal 0.5–4.5 mIU/L) and free T4 0.5 ng/dL (normal 0.8–1.9 ng/dL). She feels consistently rundown and has dry skin that does not respond to the use of hand creams. Which is the best drug for initial treatment of her condition? A. Levothyroxine. B. Liothyronine. C. Desiccated thyroid. D. Methimazole. D. Hypothyroid Disorders 1. Classification a. Hashimoto disease: Most common hypothyroid disorder in areas with iodine sufficiency i. Autoimmune-induced thyroid injury resulting in decreased thyroid secretion ii. Disproportionately affects women b. Iatrogenic: Thyroid resection or radioiodine ablative therapy for hyperthyroidism c. Iodine deficiency most common cause worldwide d. Secondary causes i. Pituitary insufficiency (failure to produce adequate TSH secretion, called by some a central or secondary hypothyroidism) ii. Drug induced (e.g., amiodarone, lithium) 2. Diagnosis a. Low free T4 serum concentrations b. Elevated TSH concentrations, typically seen as first laboratory abnormality, usually greater than 10 mIU/L (normal or low if central hypothyroidism is the cause) c. Thyroid antibodies such as antithyroid peroxidase and antithyroglobulin autoantibodies d. Screen patients older than 60, especially women (many different screening recommendations are given by various professional groups with little consensus). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-208 Endocrine and Metabolic Disorders 3. Clinical presentation a. Cold intolerance b. Dry skin c. Fatigue, lethargy, weakness d. Weight gain e. Bradycardia f. Slow reflexes g. Coarse skin and hair h. Periorbital swelling i. Menstrual disturbances (more frequent or longer menstruation, painful menstruation, menorrhagia) caused by hypometabolism of estrogen j. Goiter (primary hypothyroidism) 4. Therapy goals a. Minimize or eliminate symptoms; improve quality of life b. Minimize long-term damage to organs (myxedema coma, heart disease) c. Normalize free T4 and TSH concentrations 5. Therapeutics a. Levothyroxine (drug of choice) i. Mechanism of action: Synthetic T4 ii. Dosing (a) Initial (1) In otherwise healthy adults, 1.6 mcg/kg (use ideal body weight) per day (2) In patients age 50–60, consider 50 mcg/day. (3) In those with existing cardiovascular disease, consider 12.5–25 mcg/day. (b) For optimal bioavailability, usually dosed in the morning on an empty stomach 30–60 minutes before breakfast or at bedtime 3–4 hours after last meal; dosed separately from other medications (particularly calcium or iron supplements and antacids) (c) Dosage titration depending on response (control of symptoms, normalization of TSH and free T4) (d) Can increase or decrease in 12.5- to 25-mcg/day increments, or consider increase or decrease in 10%–15% of weekly dose (e) Daily requirements are higher in pregnancy (separate guidelines available for treating thyroid disorders in pregnancy). (f) For hospitalized patients already receiving levothyroxine but for whom oral administration not an option, the intravenous dose is 75% of the oral dose. iii. Monitoring (a) 4–8 weeks is appropriate to assess patient response in TSH after initiating or changing therapy (about a 7-day half-life for T4). May take longer for TSH to achieve steady-state concentrations (b)  Use free T4 rather than TSH if central or secondary hypothyroidism; obtain sample before daily dosing of levothyroxine iv. Adverse effects (a) Hyperthyroidism (b) Cardiac abnormalities (tachyarrhythmias, angina, myocardial infarction) (c) Linked to risk of fractures (usually at higher dosages or over-supplementation) v. Efficacy: If levothyroxine is properly dosed, most patients will maintain TSH and free T4 in the normal ranges and experience symptomatic relief. vi. Considered drug of choice because of its adverse effect profile, cost, lack of antigenicity, and uniform potency ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-209 Endocrine and Metabolic Disorders vii. Bioequivalence (a) Guidelines recommend brand-name levothyroxine or consistent use of specific generic product. (b) TSH concentrations in bioequivalence testing were never obtained; small changes in T4 between products can significantly change the TSH. Pharmacokinetic studies were conducted in healthy subjects with normal thyroid function. b.  Liothyronine (synthetic T3), liotrix (synthetic T4/T3), and desiccated thyroid are not recommended by leading professional organizations or clinical guidelines. If converting from dessicated thyroid preparation to levothyroxine, 60 mg of dessicated thyroid is about equal to 100 mcg of levothyroxine. E. Subclinical Hypothyroidism 1. Definition: Elevated TSH (above upper limit of reference range) with normal T4. Often the result of early Hashimoto disease 2. Risk a. TSH greater than 7 mIU/L in older adults associated with elevated risk of heart failure b. TSH greater than 10 mIU/L associated with elevated risk of coronary heart disease 3. Treatment of subclinical hypothyroidism is controversial because benefits in identified patients are inconclusive. An association between the use of levothyroxine and a reduction in heart disease in younger patients (40–70 years of age) does appear to exist, but not in older patients (older than 70). 4. Whom to treat a. TSH 10 mIU/L or greater b. TSH 4.5–10 mIU/L and i. Symptoms of hypothyroidism ii. Antithyroid peroxidase antibodies present iii. History of cardiovascular disease, heart failure, or risk factors for such c. Initial daily doses of 25–75 mcg of levothyroxine recommended 5.  If untreated, screen regularly for the development of overt hypothyroidism (decreased free T4 concentrations). F. Myxedema Coma 1. Severe and life-threatening decompensated hypothyroidism; mortality rate 30%–60% 2. Precipitating causes: Trauma, infections, heart failure, medications (e.g., sedatives, narcotics, anesthesia, lithium, amiodarone) 3. Presentation: Coma is not required and is uncommon, despite terminology; altered mental state (very common); diastolic hypertension; hypothermia; hypoventilation 4. Pharmacotherapy a. Intravenous thyroid hormone replacement i.  T4: 200- to 400-mcg intravenous loading dose, followed by 1.6 mcg/kg daily. Lower the initial dose in frail patients or patients with established cardiovascular disease. Intravenous doses are around 75% of oral administration. ii. Some advocate the use of T3 over T4, given that T3 is more biologically active and that T4/T3 conversion may be suppressed in myxedema coma. Cost and availability limit intravenous T3 use. b. Antibiotic therapy: Given common infectious causes, some clinicians advocate empiric therapy with broad-spectrum antibiotics. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-210 Endocrine and Metabolic Disorders c. d. Corticosteroid therapy i. Hydrocortisone 100 mg every 8 hours (or equivalent steroid) or doses appropriate for the stressed state ii. Can be discontinued if random cortisol concentration not depressed Adjust levothyroxine dose on the basis of serum T3 measured every 1 or 2 days. II. PITUITARY GLAND DISORDERS Table 1. Basic Pituitary Gland (Anterior) Hormone Physiology Anterior Primary Pituitary Hormone Function(s) Growth hormone (GH) Promote tissue growth Hypothalamic Stimulator GH-releasing hormone Adrenocorticotropic hormone (ACTH) Thyroid-stimulating hormone (TSH) Prolactin Stimulate adrenal cortisol and androgen release Metabolic stability Follicle-stimulating hormone Luteinizing hormone Maturation of ovarian follicles Sperm production Secretion of sex steroids Corticotropin-releasing hormone Thyrotropin-releasing hormone Thyrotropin-releasing hormone Gonadotropin-releasing hormone Gonadotropin-releasing hormone Regulate lactation Primary Secretion Inhibitor Somatostatin Insulin-like growth factor-1 Cortisol Triiodothyronine Dopamine Inhibin Estrogens Estrogens and progestins Testosterone A. Classification (focus on the common anterior pituitary disorders) 1. Hypersecretory diseases a. Acromegaly and gigantism: Usually caused by growth hormone (GH)-secreting pituitary adenoma b. Hyperprolactinemia i. Most common cause is prolactinomas (prolactin-secreting pituitary tumor). ii. Drug induced (e.g., serotonin reuptake inhibitors and some antipsychotics) iii. Central nervous system lesions 2. Hyposecretory disease a. GH deficiency i. Congenital abnormality caused by GH gene deletion, GH-releasing hormone deficiency ii. Other causes are pituitary aplasia, head trauma, and central nervous system infection. iii. Idiopathic b. Panhypopituitarism: Result of partial or complete loss of anterior and posterior pituitary function. Can be caused by primary pituitary tumor, ischemic necrosis of the pituitary, trauma from surgery, or irradiation. Results in adrenocorticotropic hormone (ACTH) deficiency, GH deficiency, hypothyroidism, gonadotropin deficiency B. Acromegaly 1. Diagnosis and clinical presentation a. Failure of an oral glucose tolerance test (OGTT) to suppress GH serum concentrations but with elevated IGF-1 (GH serum concentrations alone are unreliable, given the pulsatile pattern of release in the body.) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-211 Endocrine and Metabolic Disorders b. Clinical presentation (Note that the disease has a slow onset, and many symptoms do not appear for years.) i. Excessive sweating ii. Osteoarthritis, joint pain, paresthesias, or neuropathies iii. Coarsening of facial features iv. Increased hand volume or ring size, increased shoe size v. Hypertension, heart disease, cardiomyopathy vi. Sleep apnea vii. T2D 2. Therapy goals a. Reduce GH and IGF-1 concentrations b. Decrease mortality c. Improve clinical symptoms d. Normalize IGF-1 concentrations and suppressed GH concentrations after OGTT 3. Therapeutics a. Treatment of choice is surgical resection of tumor, if causative. b. Pharmacotherapy usually reserved for: i. Control before surgery or irradiation ii. When surgery is not possible (usually requires lifelong pharmacotherapy) iii. Surgical failures or relapses after period of remission after surgery c. Dopamine agonists (e.g., bromocriptine, cabergoline) i. Mechanism of action: Dopamine agonist that, in acromegaly, causes paradoxical decrease in GH production ii. Dosing (bromocriptine is most commonly used agent) (a) Initial: 1.25 mg/day by mouth (b) Maximal: 20–30 mg/day (can titrate once or twice weekly, as needed) iii. Adverse effects (a) Fatigue, dizziness, nervousness (b) Diarrhea, abdominal pain iv. Efficacy: Normalization of IGF-1 concentrations in about 10% of patients. More than 50% of patients experience symptomatic relief. d. Somatostatin analog (e.g., octreotide) i. Mechanism of action: Blocks GH secretion; 40 times more potent than endogenous somatostatin ii. Dosing (a) Initial: 50–100 mcg subcutaneously every 8 hours or 20 mg orally twice daily (Oral use is typically reserved for patients who require long-term maintenance and have responded to injectable octreotide) (b) Maximal: Little benefit greater than 600 mcg/day or 80 mg daily with oral administration (c) If response is adequate, can be changed to long-acting octreotide formulation administered once monthly (d) Orally with a glass of water on an empty stomach at least 1 hour before a meal or at least 2 hours after a meal iii. Adverse effects (a) Diarrhea, nausea, cramps, flatulence, fat malabsorption (b) Arrhythmias (c) Hypothyroidism (d) Biliary tract disorders (e) Changes in serum glucose concentrations (usually reduces) ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-212 Endocrine and Metabolic Disorders iv. E  fficacy: 50%–60% of patients experience normalization of IGF-1 concentrations with good symptomatic relief as well. May shrink tumor mass in some patients e. GH receptor antagonist (e.g., pegvisomant) i. Mechanism of action: GH derivative binds to liver GH receptors and inhibits IGF-1 ii. Dosing (a) Initial: 40 mg once-daily subcutaneous injection loading dose and then 10 mg once daily (b) Maximal: 30 mg/day iii. Adverse effects (a) Nausea, vomiting (b) Flulike symptoms (c) Reversible elevations in hepatic transaminase iv. Efficacy: More than 95% of patients attain normal IGF-1 concentrations, and most have improved symptoms. Patient Case 3. A 28-year-old woman presents with acne, facial hair growth, and irregular menses that have lasted for 6–7 months. Her medical history includes hypertension and depression. Her pituitary and thyroid tests results have been negative. Her current medications include amlodipine and fluoxetine. Her prolactin concentration today is 112 ng/mL (normal 15–25 ng/mL). Which is the most likely cause of her elevated prolactin concentration? A. Amlodipine. B. Prolactin-secreting adenoma. C. Pregnancy. D. Fluoxetine. C. Hyperprolactinemia 1. Causes a. Direct: Pituitary tumor (lactotroph adenoma = prolactinoma accounting for around 40% of tumors) b. Indirect: Drug induced (most common nontumor cause), renal failure, hypothyroidism, breastfeeding c. Potential causative drugs: Typical antipsychotics, opiates, non-dihydropyridine calcium channel blockers, antidepressants 2. Diagnosis and clinical presentation a. Elevated serum prolactin concentrations; may be challenging to find specific cause (unless drug induced) b. Clinical presentation i. Amenorrhea, anovulation, infertility, hirsutism, and acne in women ii. Erectile dysfunction, decreased libido, gynecomastia, and reduced muscle mass in men iii. Headache, visual disturbances, bone loss 3. Therapy goals a. Normalize prolactin concentrations b. Normalize gonadotropin secretion c. Relieve symptoms d. Decrease tumor size 4. Therapeutics a. Surgical resection of tumor, if tumor is very large, causes severe compression of adjacent tissues, or patient does not respond to pharmacotherapy ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-213