Deja Review Pharmacology, 2nd Edition

CHAPTER 9. Endocrine Agents




What are the two general categories of drugs that are used to treat diabetes mellitus?


  1. Insulin
  2. Oral hypoglycemic agents


Which type of diabetes mellitus is each of the following statements referring to?

Loss of pancreatic β-cells

Type 1

Usually early onset

Type 1

Decreased response to insulin

Type 2

Ketoacidosis prone

Type 1

Usually adult onset

Type 2

Not ketoacidosis prone

Type 2

Absolute dependence on insulin

Type 1

May be controlled by diet and oral hypoglycemics alone

Type 2

Usually thin

Type 1

Usually obese

Type 2

Islet cell antibodies

Type 1

Near 100% concordance in monozygotic twins

Type 2

What types of drugs can elevate blood glucose concentrations?

Alcohol; β-adrenergic blockers; calcium channel blockers; combination oral contraceptives; diazoxide; diuretics; corticosteroids; lithium; niacin; phenytoin; sympathomimetics

What are the signs and symptoms of diabetic ketoacidosis?

Kussmaul respirations; fruity breath; abdominal pain; nausea; vomiting; polyuria; polydipsia; dehydration; fatigue

What chemical is responsible for causing “fruity breath” during ketoacidosis?


What are the three ketones made during ketoacidosis?


  1. β-Hydroxybutyric acid
  2. Acetoacetic acid
  3. Acetone


What is the term used to describe a rise in blood glucose usually between 4 and 11 AM due to the release of growth hormone, cortisol, glucagons, and epinephrine?

Dawn phenomenon. To determine the cause of elevated morning blood sugars, the patient must measure their glucose levels throughout the night. Then alterations in diet, medication doses, or medication choice may be made.

What is the term used to describe a rebound rise in morning blood glucose secondary to a low overnight blood glucose?

Somogyi effect. This usually results from hyperinsulinemia which decreases blood glucose. Glucagon is released when the patient becomes hypoglycemic, which causes a rebound spike in blood glucose levels. Decreasing the evening insulin dose is first-line therapy.

For each of the following types of insulin give the time of onset, peak effect, and duration:


0.17 to 0.33 hours; 1 to 3 hours; 3 to 5 hours


0.25 hours; 0.5 to 1.5 hours; 6 to 8 hours


0.5 to 1 hours; 2 to 3 hours; 8 to 12 hours

NPH (isophane insulin suspension)

1 to 1.5 hours; 4 to 12 hours; 24 hours

Lente (insulin zinc suspension)

1 to 2.5 hours; 8 to 12 hours; 18 to 24 hours

Ultralente (extended insulin zinc suspension)

4 to 8 hours; 16 to 18 hours; > 36 hours


No peak; duration is 24 hours

Can insulin glargine be mixed with other insulins?


What is the most common side effect of insulin?


What are the signs and symptoms of hypoglycemia?

Confusion; diaphoresis; tremors; tachycardia; seizures; coma; lethargy

Which sign/symptom of hypoglycemia is not masked by β-adrenergic antagonists?


What is the name of the incretin mimetic that increases insulin secretion, slows gastric emptying, and decreases food intake?


What is the name of the human amylin analog that is cosecreted with insulin and reduces postprandial glucose by prolonging gastric emptying time, reduces postprandial glucagon secretion, and suppresses appetite?


What hypoglycemic agent is not contraindicated in a pregnant woman with diabetes mellitus?


Other than blood glucose reduction, regular insulin can also be used for what condition?

Hyperkalemia. Insulin causes an intracellular shift of potassium. Insulin is given in combination with glucose to prevent hypoglycemia in this situation.

For each of the following oral hypoglycemic agents, state which drug class it belongs to?


First-generation sulfonylurea


First-generation sulfonylurea


First-generation sulfonylurea


Second-generation sulfonylurea


Second-generation sulfonylurea


Second-generation sulfonylurea


D-phenylalanine derivative






α-Glucosidase inhibitor


α-Glucosidase inhibitor








Amylin analog



For each of the following drug classes, give the mechanism of action:


Block adenosine triphosphate (ATP)-dependent potassium channels, thereby depolarizing pancreatic β-cells which lead to insulin release (release mediated via calcium influx); insulin secretagogue


Bind to nuclear peroxisome proliferator activating receptor-gamma (PPAR-γ) which leads to increased sensitization of cells to insulin; decrease hepatic gluconeogenesis; upregulate insulin receptors

D-phenylalanine derivatives

Newest insulin secretagogue which closes the potassium channels on the β-cells leading to a rapid but short-acting release of insulin

α-Glucosidase inhibitors

Inhibit intestinal amylase and α-glucosidase causing a delay in the breakdown of complex carbohydrates into glucose which subsequently delays glucose absorption, thereby lowering postprandial glucose levels


Decrease hepatic gluconeogenesis; increase tissue sensitivity to insulin


Nonsulfonylurea insulin secretagogue

Amylin analogs

Suppresses glucagon release, delays gastric emptying, decreases hunger


Synthetic glucagon-like-polypeptide (GLP-1) analogs which potentiates glucose-mediated insulin release, decreases postprandial glucagon release, decreases gastric emptying, decreases hunger

What are the side effects of the sulfonylureas?

Hypoglycemia; cross-reaction with sulfonamide allergy; weight gain

What is the longest acting sulfonylurea?


Which sulfonylurea can cause disulfiram-like reactions?


Which sulfonylurea can cause syndrome of inappropriate secretion of antidiuretic hormone (SIADH)?


The dose of what second-generation sulf onylurea should be decreased in patients with renal dysfunction?


The dose of what second-generation sulf onylurea should be decreased in patients with hepatic dysfunction?


What are the side effects of the thiazolidinediones (TZDs)?

Edema; congestive heart failure (CHF) exacerbation; weight gain; hepatotoxicity; macular edema (rare); increased bone fractures in women due to diminished osteoblast formation

Name two concomitant health conditions in which TZDs may not be used in a diabetic patient.


  1. CHF
  2. Liver failure


What are the side effects of the biguanides?

Diarrhea; lactic acidosis; decreased vitamin B12; abnormal taste

What are the side effects of the meglitinides?

Hypoglycemia; upper respiratory tract infection

What are the side effects of the α-glucosidase inhibitors?

Abdominal cramping; diarrhea; flatulence

What drug with positive inotropic and chronotropic activity can be used to stimulate the heart during a β-blocker overdose?


Based on liver function test (LFT) results, when should therapy with a thiazolidinedione be withheld?

When LFTs rise above 2.5 times the upper limit of normal

What oral hypoglycemic should be withheld when the serum creatinine is above 1.5 for males and 1.4 for females?


When used alone, can TZDs cause hypoglycemia?

No, TZDs do not cause hypoglycemia.

When used alone, can biguanides cause hypoglycemia?

No, biguanides do not cause hypoglycemia.

What time of day should meglitinides be given?

15 to 30 minutes before each meal

Would oral sucrose be effective in a hypoglycemic patient who is currently taking an α-glucosidase inhibitor?

No, it would not because sucrose is a disaccharide whose absorption is competitively blocked by the α-glucosidase inhibitors.

Would oral glucose be effective in a hypoglycemic patient who is currently taking an α-glucosidase inhibitor?

Yes, it would since glucose is a monosaccharides. α-Glucosidase inhibitors do not block intestinal transporters for monosaccharides.



What are the two types of diabetes insipidus?


  1. Neurogenic
  2. Nephrogenic


Which type of diabetes insipidus is characterized by insensitivity to vasopressin in the collecting ducts?

Nephrogenic diabetes insipidus

Which type of diabetes insipidus is characterized by inadequate secretion of vasopressin from the posterior pituitary gland?

Neurogenic diabetes insipidus

What types of drugs can cause a nephrogenic diabetes insipidus?

Lithium; demeclocycline; vincristine; amphotericin B; alcohol

What two effects does vasopressin have on the body?


  1. Antidiuresis
  2. Vasopressor


Where is theV1receptor found?

Vascular smooth muscle (causes vasoconstriction)

Where is the V2receptor found?

Renal collecting ducts (increases water permeability and reabsorption)

What is the drug of choice for neurogenic diabetes insipidus?


What is desmopressin?

Synthetic analog of vasopressin with longer half-life and no vasopressor activity (antidiuresis properties only)

What is another name for desmopressin?

l-Deamino-8-D-arginine vasopressin (DDAVP)

How is desmopressin administered?

Intranasally; orally

What are the side effects of vasopressin?

Water intoxication; hyponatremia; tremor; headache; bronchoconstriction

What is vasopressin also used for?

Esophageal varices

What is desmopressin also used for?

Hemophilia A; von Willebrand disease; primary nocturnal enuresis

How is nephrogenic diabetes insipidus treated?

Thiazide diuretics in combination with amiloride; chlorpropamide; clofibrate

What drug that can cause nephrogenic diabetes insipidus is used to treat SIADH?




What are the signs and symptoms of hyperthyroidism?

Heat intolerance; nervousness; fatigue; weight loss with increased appetite; increased bowel movements; palpitations; irregular menses; proximal muscle weakness; moist skin; fine hair; hyperactive deep tendon reflexes; tachycardia; widened pulse pressure; tremor

What are the signs and symptoms of hypothyroidism?

Growth retardation in children; slowing of physical and mental activity; weight gain; cold intolerance; constipation; weakness; depression; dry skin; cold skin; coarse skin; coarse hair; bradycardia; muscle cramps; delayed relaxation of deep tendon reflexes

What are the signs and symptoms of thyroid storm?

High fever; dehydration; delirium; tachycardia; tachypnea; nausea; vomiting; diarrhea; coma

What are the two main active thyroid hormones circulating in the body?


  1. Thyroxine (T4)
  2. Triiodothyronine (T3)


Which thyroid hormone is more active in the body?

T3 (up to five times more active)

What is the half-life of T4?

7 days

What is the half-life of T3?

1.5 days

What is the name of the enzyme that converts T4 to T 3 in the periphery?

5’-Deiodinase (5 “prime” deiodinase)

What is the name of the enzyme that converts active T4 to inactive reverse T3?


What is the drug of choice for hypothyroidism?

Levothyroxine (T4)

When a hypothyroid patient is started on levothyroxine therapy, how long will the drug take to reach a steady state?

6 to 8 weeks

What are the adverse effects of levothyroxine?

Same effects as physiologic hyperthyroidism: heat intolerance; nervousness; fatigue; weight loss with increased appetite; increased bowel movements; palpitations; irregular menses; proximal muscle weakness; moist skin; fine hair; hyperactive deep tendon reflexes; tachycardia; widened pulse pressure; tremor

What biochemical marker is used to assess for adequate thyroid replacement?

Thyroid-stimulating hormone (TSH)

What antiarrhythmic agent can potentially cause either hypothyroidism or hyperthyroidism (more commonly hypothyroidism)?

Amiodarone (contains two iodine molecules)

To which three proteins in the blood are T4 and T3 bound extensively?


  1. Thyroid-binding globulin
  2. Thyroid-binding prealbumin
  3. Albumin


The α-subunit of TSH is similar to the α-subunits of which hormones (gonadotropins) in the body?

Follicle-stimulating hormone (FSH); luteinizing hormone (LH); human chorionic gonadotropin (hCG)

What drug is used to ablate thyroid tissue?

Radioactive iodine (131I)

What drug is used to treat cardiovascular effects seen in thyrotoxicosis?


What is a side effect of surgical removal of the thyroid gland?

Hypothyroidism almost inevitably results. Other possible complications include hypocalcemia due to removal of the parathyroid glands along with the thyroid.

What are the drugs of choice to treat hyperthyroidism?

Thionamides (propylthiouracil and methimazole)

What drugs inhibit the release of preformed thyroid hormone?

Iodide; lithium

What drugs inhibit the iodination of tyrosyl residues on thyroglobulin?

Propylthiouracil; methimazole

What drugs inhibit the coupling reactions that form T3 and T4?

Propylthiouracil; methimazole; iodide

What drugs block the conversion of T4 to T3 in the periphery by inhibiting 5’-deiodinase?

Propylthiouracil; propranolol

What are the side effects of propylthiouracil and methimazole?

Pruritic maculopapular rash; vasculitis; arthralgias; fever; leukopenia; agranulocytosis

Do propylthiouracil and methimazole cross the placenta?


What is the drug of choice for hyperthyroidism in pregnancy?

Propylthiouracil (more protein bound)

What drugs can decrease levels of thyroid-binding globulin?

Androgens; glucocorticoids; L-asparaginase

What drugs can increase levels of thyroid-binding globulin?

Estrogens; perphenazine; clofibrate; fluorouracil



What are the three zones of the adrenal cortex?


  1. Zona glomerulosa (outer)
  2. Zona fasciculata (middle)
  3. Zona reticularis (inner)


Name the steroid hormones produced by each of the following layers of the adrenal cortex:

Zona glomerulosa


Zona fasciculata


Zona reticularis

Adrenal androgens

What is the major precursor of all steroid hormones?


What is the principal mineralocorticoid?


What is the principal glucocorticoid?

Cortisol, but note that cortisol does have some mineralocorticoid activity as well.

How do corticosteroids work biochemically in the body?

Bind to intracellular cytoplasmic receptors in target tissues then subsequently translocate to the nucleus where they act as transcription factors

What is the precursor of adrenocorticotropic hormone (ACTH)?

Proopiomelanocortin (POMC)

What chemicals are released when POMC is cleaved?

ACTH; lipotropin; β-endorphin; metenkephalin; melanocyte-stimulating hormone (MSH)

What drug is used to diagnose adrenal insufficiency?

ACTH (cosyntropin)

A cosyntropin stimulation test that results in no cortisol secretion characterizes which type of adrenal insufficiency?

Primary adrenal insufficiency (defect at the level of the adrenal gland)

A cosyntropin stimulation test that results in reasonable cortisol secretion characterizes which type(s) of adrenal insufficiency?

Secondary adrenal insufficiency (defect at the level of the pituitary gland) and possibly tertiary adrenal insufficiency (defect at the level of the hypothalamus)

What is the primary mechanism by which corticosteroids increase the neutrophil count?

Demargination, where the polymorphonuclear cells are detached from the endovascular wall and are therefore available to be counted in the peripheral blood smear

How is the production of arachidonic acid decreased by glucocorticoids?

Inhibition of phospholipase A2

How is Gushing syndrome diagnosed?

Dexamethasone suppression test

Give examples of short-acting glucocorticoids:

Cortisone; hydrocortisone

Give examples of intermediate-acting glucocorticoids:

Methylprednisolone; prednisone; triamcinolone

Give examples of long-acting glucocorticoids:

Betamethasone; dexamethasone

Give an example of a synthetic mineralocorticoid:


How long after initiation of glucocorticoid therapy does it take to suppress the hypothalamic-pituitary-adrenal (HPA) axis?

2 weeks

How should long-term glucocorticoid therapy be discontinued?

Taper regimen (taper regimen commonly used when discontinuing >2 weeks of glucocorticoid therapy)

How do you prevent suppression of the HPA axis while using glucocorticoids?

Alternate day dosing (every other day dosing)

List the adverse effects of glucocorticoids:

Acne; insomnia; edema; hypertension; osteoporosis; cataracts; glaucoma; psychosis; increased appetite; hirsutism; hyperglycemia; muscle wasting; pancreatitis; striae; redistribution of body fat to abdomen, back, and face

What drug inhibits glucocorticoid synthesis by inhibiting 11-hydroxylase activity?


What drug inhibits the conversion of cholesterol to pregnenolone?


What antifungal can be used to lower cortisol levels in Gushing disease and may cause gynecomastia as an adverse effect?


What diuretic blocks mineralocorticoid receptors and also inhibits the synthesis of aldosterone and androgens (eg, testosterone)?


What is the main side effect of spironolactone?

Gynecomastia; hyperkalemia

How does spironolactone work as a diuretic?

Antagonizes mineralocorticoid receptors in the kidney, thereby preventing sodium reabsorption in the distal tubules but not increasing potassium loss (therefore potassium-sparing)

Using an angiotensin-converting enzyme (ACE) inhibitor in combination with spironolactone can cause what major electrolyte abnormality?


Name a potassium-sparing diuretic that does not have anti-androgen side effects:

Eplerenone, which has increased specificity for the mineralocorticoid receptor when compared to spironolactone



Is testosterone effective when administered orally?

No, as it is inactivated by first-pass metabolism.

What enzyme converts testosterone to dihydrotestosterone (DHT)?


Where is 5-α-reductase found?

Skin; epididymis; prostate; seminal vesicles

What drug inhibits 5-α-reductase?

Finasteride; dutasteride

What are the two main therapeutic indications of finasteride?


  1. Benign prostatic hyperplasia (BPH)
  2. Male pattern baldness


What are the uses of testosterone and its derivatives (danazol; stanozolol; nandrolone; oxandrolone)?

Male hypogonadism; increase muscle mass; increase RBCs; decrease nitrogen excretion; endometriosis (not first-line therapy for endometriosis given side effects)

What are the adverse effects of testosterone?

Edema; premature closing of the epiphysis; increased aggression (“road rage”); psychosis; increased low-density lipoprotein (LDL); decreased high-density lipoprotein (HDL); cholestatic jaundice; decreased spermatogenesis; gynecomastia; increased masculinization

What antifungal drug inhibits the synthesis of androgens and is also used as an antifungal?


What drugs act as androgen receptor blockers and are used in the treatment of prostate cancer?

Flutamide; bicalutamide

Which drug act as androgen receptor blocker and is used in the treatment of stomach ulcers?

Cimetidine (a histamine H2-receptor blocker)

What is the mechanism of action of leuprolide?

Gonadotropin-releasing hormone (GnRH) agonist (daily administration suppresses LH and FSH secretion, thereby inhibiting ovarian and testicular steroidogenesis)

What are the therapeutic uses of leuprolide?

Prostate cancer; endometriosis



What is the major natural estrogen?

17-α estradiol

Where do conjugated equine estrogens (Premarin) come from?

Urine of pregnant mares

What is Premarin used for?

Vasomotor symptoms associated with menopause; vulvar and vaginal atrophy; abnormal uterine bleeding

Name two synthetic steroidal estrogens:


  1. Ethinyl estradiol
  2. Mestranol


Name one synthetic nonsteroidal estrogen:

Diethylstilbestrol (DBS)

Mestranol is metabolized to what chemical compound?

Ethinyl estradiol

What are the therapeutic uses of estrogens?

Contraception; hormone replacement therapy (HRT); female hypogonadism; dysmenorrhea; uterine bleeding; acne; osteoporosis

How do estrogens affect serum lipids?

Increased triglycerides; increased HDL; decreased LDL

How is estrogen useful in preventing osteoporosis?

Decreases bone resorption

What are the adverse effects of estrogens?

Nausea; vomiting; headache; breast tenderness; endometrial hyperplasia; cholestasis; increased blood coagulation; increased endometrial cancer risk; increased breast cancer risk

Estrogen use is contraindicated in which settings?

History of or current deep vein thrombosis (DVT); history of or current pulmonary embolism (PE); active or recent stroke; active or recent myocardial infarction (MI); carcinoma of the breast; estrogen-dependent tumors; hepatic dysfunction; pregnancy

How do estrogens increase blood coagulation?

Decrease antithrombin III; increase clotting factors II, VII, IX, and X

What can happen to the female offspring of women who took DES during pregnancy?

Clear cell cervical or vaginal adenocarcinoma

How do estrogenic compounds work as contraceptives?

Suppresses ovulation

What does the enzyme aromatase do?

Converts testosterone to estradiol

Name three aromatase inhibitors:


  1. Anastrozole
  2. Letrozole
  3. Exemestane


What are aromatase inhibitors used for?

Breast cancer

What is clomiphene used as?

Fertility drug

How does clomiphene work?

Antiestrogen that induces ovulation by inhibiting negative feedback of estrogen on the hypothalamus and pituitary (this suppression leads to increasing release of LH and FSH)

What are potential “adverse effect” of clomiphene?

Multiple births; hot flashes (10% patients); ovarian hyperstimulation (7% patients); reversible visual disturbances (2% patients)

What does SERM stand for?

Selective estrogen receptor modulator

Name two SERMs:


  1. Raloxifene
  2. Tamoxifen


What is raloxifene used for?

Prevention and treatment of osteoporosis in postmenopausal women

How does raloxifene work?

Estrogen receptor agonist in bone; estrogen receptor antagonist in breast and uterus

What is tamoxifen used for?

Breast cancer

How does tamoxifen work?

Estrogen receptor agonist in bone; estrogen receptor antagonist in breast; estrogen receptor partial agonist in uterus

Can tamoxifen increase endometrial cancer risk?

Yes, it has stimulatory effects on endometrial tissue.

Can raloxifene increase endometrial cancer risk?

No, it does not increase the risk of endometrial cancer because it has selective estrogen effects on the breast and bone but not the endometrium.

What are the adverse effects of tamoxifen?

Endometrial hyperplasia; hot flashes; nausea; vomiting; vaginal bleeding; menstrual irregularities

How does raloxifene affect serum lipids?

Decreases total and LDL cholesterol; no effect on HDL or triglycerides

What must you tell a female patient who is using hormonal contraception when she is given a prescription for antibiotics?

Antibiotics may decrease the effectiveness of OCPs; recommend the use of a “backup” contraceptive method in addition to the OCPs throughout the duration of the antibiotic course. This applies to both oral and intravenous antibiotics.

Which type of OCPs are used to shorten or suppress menstruations?

Combination OCPs

Which OCPs are used to palliate the effects of polycystic ovary syndrome (PCOS)?

Combination OCPs (often in combination with (oral) hypoglycemics)



What is the major natural progestin?


What are the therapeutic uses of progestins?

Contraception; HRT (with estrogens); control of uterine bleeding; dysmenorrhea; suppression of postpartum lactation; endometriosis

Which progestins also possess androgenic activity?

Norethindrone; norgestrel

Why is progesterone added to a HRT regimen in a female with an intact uterus?

Decrease risk of endometrial cancer by preventing unopposed action of estrogen. If the patient is status post hysterectomy then combination (estrogen + progesterone) therapy is unnecessary.

How often is depot medroxyprogesterone given?

Every 3 months (13 wk)

How long does the levonorgestrel contraceptive subdermal implant last?

5 years

What are the adverse effects of progestins?

Edema; depression; glucose intolerance; breakthrough bleeding; increased LDL; decreased HDL; hirsutism (androgenic progestins); acne (androgenic progestins)

What drug acts as a progesterone antagonist and is used in combination with prostaglandin Ej as an abortifacient?

Mifepristone (RU 486)

What are the adverse effects of mifepristone?

Abdominal cramping; uterine bleeding; pelvic infection; ectopic pregnancy

How do progestins work as contraceptives?

Prevents implantation of the early embryo into the endometrium; increases thickness of cervical mucus, thereby decreasing sperm access through the cervix



A 64-year-old man with a past medical history of hypertension, GERD, and type 2 diabetes mellitus presents to the emergency room with severe right upper quadrant pain. Acute cholecystitis is suspected and an abdominal CT with contrast ordered. Upon inspection of the patient’s medication list, the attending physician orders one of the patient’s medications to be held immediately and not resumed until at least 48 hours after the CT and adequate renal function has been ascertained. What medication was the patient taking that caused this concern?

The patient is taking metformin, a biguanide, for his diabetes. Metformin in combination with iodinated contrast materials can lead to lactic acidosis and decreased renal function. This is particularly concerning in patients who may already have some degree of renal impairment, such as diabetics. Additionally, preexisting renal impairment in combination with oral contrast can lead to increased serum levels of metformin, leading to toxicity. Therefore, it is imperative that the medication be stopped before use of the contrast medium and not restarted for 48 hours following the procedure. Proper kidney function needs to be documented as well before the medication is resumed.

A 24-year-old woman with no significant past medical history is being evaluated at a prenatal visit. Her husband accompanies her. The husband, who happens to be balding, quips with the doctor, “I know I look too old to be the daddy, but by the time the baby gets here I’m going to look ten years younger. I’m taking this great new medication that is making all my hair grow back.” The obstetrician shows mild concern and asks exactly what medication the man is taking. What medication used to treat male pattern baldness must be avoided around pregnant women?

Finasteride, a 5-α-reductase inhibitor has been shown to be effective to treat some cases of male pattern baldness. Different formulations of the drug exist in various doses. Some patients will buy the less expensive brand of the drug and split the tablets to get the appropriate dose. This is a hazardous practice around pregnant females since even contact with crushed or broken tablets can lead to birth defects, notably abnormalities of the male external genitalia. In light of the potential adverse effects, the obstetrician could replace finasteride with topical minoxidil, which opens potassium channels and stimulates hair growth by an unknown mechanism.

A 19-year-old man presents to his primary care physician with complaints of increasing fatigue. He has occasional dizziness and feels weak. He believes recently he has contracted the flu because he has had nausea and vomiting, as well as muscle pain. He states that he has to be careful not to stand up too quickly, as this makes his dizziness worse. In-office evaluation reveals a thin adult male. Orthostatics are positive. The physician also notes a general darkening of the patient’s skin, especially in the skin creases. Electrolyte tests are ordered. What other diagnostic test would be appropriate at this time, and what would be the likely results?

The hyperpigmentation here is a red flag for Addison disease, or primary adrenal insufficiency. Decreased output of cortisol from the adrenals leads to a compensatory increase in corticotrophin-releasing hormone (CRH) from the hypothalamus, leading to release of POMC, the precursor of ACTH, from the anterior pituitary. POMC is cleaved into ACTH and melanocyte-stimulating hormone, thus leading to increased skin pigmentation in patients suffering from Addison disease. Decreased levels of the stress hormone cortisol account for the patient’s other symptoms. To ascertain the primary nature of the disease, an ACTH (or cosyntropin) stimulation test should be ordered. A failure to produce an increase in serum levels of cortisol at either low or high doses of ACTH indicates failure at the level of the adrenal glands, or primary adrenal insufficiency. On physical examination, the hyperpigmentation of Addison disease may be distinguished from a suntan by examining areas unlikely to be exposed to sun, such as the axilla. Skin creases also tend to be darkly pigmented in Addison disease, as seen in this patient.