TOP SECRETS

Michael T. McDermott

1. Type 1 diabetes is caused by autoimmune destruction of pancreatic beta cells resulting in absolute
insulin deficiency. Type 2 diabetes is the consequence of a combination of insulin resistance and
progressive beta-cell failure.
2. Diabetic patients should be treated to standards based on scientific evidence: hemoglobin A1C lower
than 7%, low-density lipoprotein (LDL) cholesterol lower than 100 mg/dL, and blood pressure lower
than 130/80 mm Hg. However, the goals must be individualized to be appropriate for the patient’s
age, duration of diabetes, risk of hypoglycemia, comorbidities, and life expectancy.
3. Microvascular complications of diabetes mellitus are directly related to hyperglycemia and result
from the formation of advanced glycation end products, polyol accumulation, protein kinase C
activation, accrual of intracellular glucosamine, and oxidative stress.
4. The propensity for developing vascular disease in type 2 diabetes is likely related to insulin resis-
tance and the pathologic clustering of dyslipidemia and hypertension inherent in this condition.
5. Intensive insulin therapy, or basal-bolus therapy, mimics normal pancreatic insulin secretion. Basal
insulin is the amount required to regulate hepatic glucose production between meals, whereas
bolus insulin is given to match mealtime carbohydrate intake, by using a carbohydrate-to-insulin
ratio and a hyperglycemic correction factor with each meal.
6. Insulin is the best medication for managing hyperglycemia in hospitalized patients. In intensive care
patients, intravenous insulin infusions are superior to subcutaneous insulin regimens in achieving
quick and appropriate glycemic control.
7. Scheduled target-based regimens of basal insulin and short-acting insulin analogs are the safest
and most effective way to treat inpatient hyperglycemia. Sliding scale regular insulin regimens
cause more hyperglycemia and hypoglycemia and should be abandoned.
8. Women who develop gestational diabetes have approximately a 50% risk of developing type 2
diabetes mellitus within 5 to 10 years.
9. Normalizing the hemoglobin A1C in diabetic women before pregnancy and during the first 10 weeks
of organogenesis can reduce the fetal major malformation rate from 25% to 2% to 3%.
10. Elevated LDL cholesterol and low high-density lipoprotein (HDL) cholesterol are major risk factors
for coronary artery disease (CAD). Serum triglyceride levels greater than 150 mg/dL are also asso-
ciated with CAD, whereas levels greater than 1000 mg/dL increase the risk of acute pancreatitis.
11. Statins are the most effective LDL cholesterol–lowering agents and have the best evidence base
for reducing cardiovascular events. Additional LDL reduction can be achieved by adding ezetimibe,
niacin, and bile acid resins.
12. Fibrates are the most effective triglyceride-lowering agents, but additional reductions can be
achieved by adding niacin, fish oils, and high-dose statins.
13. Metabolic syndrome is a major CAD risk factor complex consisting of any three of the following:
abdominal obesity, hypertension, hypertriglyceridemia, low HDL cholesterol, and hyperglycemia.
14. Obesity, defined as a body mass index (BMI) greater than 30 kg/m2, is associated with an increased
risk of developing related medical illnesses, including diabetes mellitus, hypertension, CAD, pulmo-
nary emboli, sleep apnea, and osteoarthritis.
15. Diet and exercise to alter energy balance are the mainstays of obesity management, but phen-
termine, phentermine plus topiramate (Qsymia), lorcaserin (Belviq), and orlistat (Xenical) are
medications currently approved by the Food and Drug Administration (FDA) that can be used to
help overweight and obese patients lose weight.

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16. Adequate intake of calcium (1000–1500 mg/day) and vitamin D (800–1200 units/day), regular
exercise, smoking cessation, and limitation of alcohol and caffeine consumption should be advised
for people who want to prevent osteoporosis and for patients who are being treated with osteopo-
rosis medications.
17. Osteoporosis medication is advised for all patients who have sustained a fragility fracture, who
have a bone density T-score of less than 22.5, or who have a 10-year hip fracture risk higher than
3% or a major osteoporosis fracture risk higher than 20% according to the FRAX tool, developed by
the World Health Organization (WHO).
18. Osteoporosis medications fall into two main categories: antiresorptive agents and anabolic agents.
Antiresorptive agents include bisphosphonates, denosumab, estrogen, selective estrogen receptor
modulators, and calcitonin. Teriparatide is the only anabolic agent available.
19. Glucocorticoid-induced osteoporosis results from a combination of suppressed bone formation and
accelerated bone resorption, thus accounting for the rapid bone loss seen in glucocorticoid-treated
patients.
20. The American College of Rheumatology recommends therapy for all patients who will be treated or
have been treated with 7.5 mg/day or more of prednisone (or equivalent) for 3 months or longer.
The National Osteoporosis Foundation recommends treatment at 5 mg or more daily of prednisone.
21. The forearm is the most important site for bone mass measurement in patients with hyperpara-
thyroidism.
22. Osteomalacia and rickets result from inadequate or delayed mineralization of bone.
23. The causes of osteomalacia and rickets fall into three categories: (1) abnormal vitamin D supply,
metabolism, or action; (2) abnormal phosphate supply or metabolism; and (3) a small group of
disorders characterized by normal vitamin D and mineral metabolism.
24. Paget’s disease, which is likely caused by a combination of genetic and environmental factors, is
characterized by abnormal bone architecture resulting from an imbalance between osteoclastic
bone resorption and osteoblastic bone formation.
25. Bisphosphonates are the most effective treatment for Paget’s disease of bone.
26. Although there are more than 30 major causes of hypercalcemia, hyperparathyroidism and hyper-
calcemia of malignancy account for greater than 90%. Measuring a serum parathyroid hormone
(PTH) level reliably differentiates these two disorders.
27. Calcimimetic medications bind to the calcium sensor receptor and suppress PTH secretion. Cinacalcet
is FDA approved for the treatment of primary and secondary hyperparathyroidism and parathyroid
carcinomas.
28. Primary hyperparathyroidism is associated with hypercalcemia, osteoporosis, nephrolithiasis, and
symptoms associated with these conditions.
29. The recommendations for surgery in patients with asymptomatic hyperparathyroidism are as
follows: serum calcium greater than 1 mg/dL above the upper normal limit, decreased creatinine
clearance less than 70% of age-matched normal persons, reduced bone density with a T-score
lower than 22.5, and age less than 50 years. Surgery is also recommended for patients with
symptoms or with calcium nephrolithiasis.
30. Hypercalcemia of malignancy is most often secondary to tumor production of PTH-related protein
(PTHrp), which binds to PTH/PTHrp receptors and stimulates bone resorption, thus causing
hypercalcemia.
31. Hypocalcemia is a frequent problem in intensive care settings and is often a result of intravenous
medications and/or transfusions.
32. Calcitriol (1,25-dihydroxyvitamin D) is the treatment of choice for hypocalcemia in patients with
hypoparathyroidism or renal failure.
33. Kidney stones form because of supersaturation of urinary stone precursors (e.g., calcium and
oxalate), insufficient stone inhibitors (e.g., citrate), abnormal urine pH, or insufficient urine volume.
34. Prevention of kidney stones includes daily intake of 2 liters of fluid, increased intake of citrate-
containing drinks, and no more than 1000 to 1200 mg of calcium, 2300 mg of sodium, and 1 g/kg
ideal body weight of protein. Excessive calcium, oxalate, vitamin D, and grapefruit juice should be
avoided.
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35. Thyroid hormone replacement in a hypothyroid patient with unsuspected, coexistent primary or
secondary adrenal deficiency may precipitate an acute adrenal crisis.
36. Aldosterone deficiency generally does not occur in hypopituitarism because the principal physiologic
regulator of aldosterone secretion is the renin-angiotensin system.
37. Nonfunctioning pituitary tumors produce symptoms primarily by mass effects: optic chiasm
compression, cavernous sinus invasion, erosion into the bony sella turcica, and compression or
destruction of the pituitary stalk or gland causing hypopituitarism.
38. Pituitary tumors that do not produce detectable levels of pituitary hormones may raise serum pro-
lactin levels modestly by pituitary stalk compression, which interferes with the flow of dopamine
from the hypothalamus.
39. Treatment for nonfunctioning pituitary tumors larger than 1.0 cm consists of transsphenoidal surgery
with subsequent close monitoring for tumor recurrence or regrowth. Radiation therapy may be a
useful adjunctive therapy for incompletely resected tumors.
40. A prolactin level greater than 200 ng/mL almost always indicates a prolactin-secreting tumor, except
during late pregnancy.
41. Prolactin elevation often causes galactorrhea and amenorrhea in women and hypogonadism in men.
Another important consequence of elevated prolactin is decreased bone mineral density, which is not
always completely reversible.
42. Acromegaly is caused by a pituitary tumor that secretes excess growth hormone, which causes
damage to bones, joints, the heart, and other organs and is associated with considerable morbidity
and excess mortality.
43. The best screening test for acromegaly is a serum insulin-like growth factor-I (IGF-I) level.
44. Glycoprotein-secreting pituitary tumors include gonadotropinomas (secreting luteinizing hormone
[LH] or follicle-stimulating hormone [FSH]) and TSHomas (secreting thyroid-stimulating hormone
[TSH]). These tumors are frequently quite large.
45. Hyperthyroid patients with detectable serum TSH levels should always be evaluated for inappropriate
TSH secretion (either a TSHoma or thyroid hormone resistance).
46. Cushing’s syndrome screening tests (urinary cortisol, salivary cortisol, overnight 1-mg dexamethasone
suppression test) can be misleading, and repeated testing or more extensive confirmatory testing is
often needed.
47. Most patients with Cushing’s syndrome have a small pituitary tumor producing adrenocorticotropic
hormone (ACTH).
48. Rapid changes in body water amount or distribution can cause severe neurologic dysfunction and
are reflected clinically by hyponatremia or hypernatremia. Treatment requires a clear understanding
of changes in plasma sodium, plasma osmolality, and effective circulating volume.
49. Identification of growth abnormalities in children requires accurate height measurements and plot-
ting against appropriate standards.
50. Growth abnormalities in children are most commonly the result of normal growth variants or
chronic medical problems. Hormonal abnormalities are less common causes.
51. Long-term abuse of supraphysiologic growth hormone doses may lead to the following: features of
acromegaly; osteoarthritis; irreversible bone and joint deformities; increased vascular, respiratory,
and cardiac abnormalities; hypogonadism; diabetes mellitus; and abnormal lipid metabolism.
52. Spontaneous or easily provoked hypokalemia in a hypertensive patient should suggest the possibil-
ity of primary hyperaldosteronism.
53. The best screen for primary hyperaldosteronism is a ratio of plasma aldosterone to plasma renin
activity (PA/PRA ratio) greater than 20. Most cases of primary hyperaldosteronism result from bilat-
eral adrenal hyperplasia (idiopathic hyperaldosteronism).
54. Episodic headache, diaphoresis, and palpitations in a hypertensive patient suggest pheochromocytoma.
55. Pheochromocytomas are 10% bilateral, 10% extraadrenal, 10% familial, and 10% malignant.
56. Features that suggest malignancy in an adrenal tumor are size larger than 6 cm, heterogeneity,
calcifications, irregular borders, local invasion, lymphadenopathy, decreased lipid content
(Hounsfield units greater than 20), or elevated levels of serum androgens or urinary or plasma
dopamine.
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57. Incidentally discovered adrenal masses should be evaluated for evidence of malignancy (size
. 6 cm or progressive growth) and excess hormone secretion (cortisol, aldosterone, androgens,
catecholamines).
58. Adrenal insufficiency should be suspected in outpatients who have received supraphysiologic doses
of glucocorticoids for more than 1 month, in intensive care unit patients who are hemodynamically
unstable despite aggressive fluid resuscitation or who have septic shock, or in any patient with
signs or symptoms suggesting adrenal insufficiency.
59. Adrenal crisis should be treated aggressively using normal saline solution with 5% dextrose,
intravenous glucocorticoids (dexamethasone if treating before drawing random cortisol and ACTH;
hydrocortisone afterwards), other supportive care, and a search for the precipitating illness.
60. Congenital adrenal hyperplasia (CAH), the most common inherited disease, is a group of autosomal
recessive disorders, the most frequent of which is 21-hydroxylase deficiency. The most serious
consequences of CAH are ambiguous genitalia in female infants at birth, neonatal salt wasting,
premature puberty, and short stature as an adult.
61. Radioactive iodine uptake (RAIU) is used primarily to determine whether patients with thyrotoxicosis
have a high-RAIU disorder or a low-RAIU disorder.
62. A thyroid scan is used to distinguish among the three types of high-RAIU thyrotoxicoses (Graves’
disease, toxic multinodular goiter, toxic nodule) and to determine whether thyroid nodules are
nonfunctioning (cold), eufunctioning (warm), or hyperfunctioning (hot).
63. Older patients with thyrotoxicosis may not have classical hyperadrenergic symptoms and signs, but
may instead present with weight loss, depression, or heart disease (worsening angina pectoris, atrial
fibrillation, congestive heart failure). This picture is often referred to as apathetic thyrotoxicosis.
64. Radioiodine treatment may worsen eye disease in patients with significant proptosis or periorbital
inflammation resulting from Graves’ ophthalmopathy. If radioiodine is used, patients should stop
smoking and should take a course of oral corticosteroids immediately after the radioiodine
treatment.
65. Levothyroxine is the preferred initial treatment for hypothyroidism. Healthy young patients can be
started at a dose of 1.6 mg/kg/day, but in patients more than 60 years old and in those with CAD, a
starting dose of 25 mg/day is preferable.
66. The goal TSH for treatment of primary hypothyroidism in most people is between 0.5 and 2.0 mU/L.
67. Amiodarone-induced thyroid disease (AITD) may be caused by iodine-induced hyperthyroidism (type
1 AITD) or destruction-induced thyroiditis (type 2 AITD).
68. Fine-needle aspiration (FNA) of thyroid nodules is a safe outpatient procedure with an accuracy of
90% to 95% in determining malignancy.
69. Toxic thyroid adenomas are rarely cancerous.
70. Thyroglobulin is the best tumor marker for monitoring differentiated thyroid cancer.
71. Suppression of TSH, a thyroid cancer growth factor, with levothyroxine is an important therapeutic
intervention in patients with differentiated thyroid cancer.
72. Thyroid storm is a life-threatening condition that must be aggressively treated with antithyroid
drugs, cold iodine, beta-blockers, stress glucocorticoid doses, and management of any precipitating
factors.
73. Myxedema coma is a potentially fatal condition that should be treated promptly with rapid repletion
of the thyroid hormone deficit with levothyroxine with or without liothyronine, glucocorticoids, and
treatment of any precipitating causes.
74. The euthyroid sick syndrome is not a thyroid disorder, but is instead a group of changes in serum
thyroid hormone and TSH levels that result from cytokines and inflammatory mediators produced in
patients with nonthyroidal illnesses.
75. The euthyroid sick syndrome appears to be an adaptive response to reduce tissue metabolism and
preserve energy during systemic illnesses. Therefore, treatment with thyroid hormone is not gener-
ally recommended but may be beneficial in patients with chronic heart failure.
76. Women with type 1 diabetes mellitus have a threefold greater risk of developing postpartum
thyroid disorders than do nondiabetic women who are positive for antithyroid peroxidase (TPO)
antibody.
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77. Postpartum thyroiditis occurs in approximately 5% of normal women and approximately 25% of
women with type 1 diabetes mellitus.
78. On average, a women’s thyroid hormone replacement dose for hypothyroidism increases by 25 to
50 mg per day during pregnancy, often during the first trimester.
79. The symptoms of hypothyroidism often mimic those of depression, whereas those of hyperthyroid-
ism may be confused with mania or depression.
80. About 20% of patients admitted to the hospital with acute psychiatric presentations, including
schizophrenia and major affective disorders, but rarely dementia or alcoholism, may have mild
elevations in their serum thyroxine (T4) levels and, less often, their triiodothyronine (T3) levels.
81. Central precocious puberty occurs more frequently in girls than boys. The condition is often idio-
pathic in girls, whereas boys with central precocity have a much higher incidence of underlying
central nervous system disorders.
82. Hypogonadism should be characterized as primary (a disorder of the testes) or secondary (a disorder
of the hypothalamic-pituitary unit). A reduction in testicular volume (, 20 mL) is the most common
manifestation of hypogonadism and is seen in nearly all cases of long-standing hypogonadism.
83. The diagnosis of hypogonadism is confirmed by a correctly obtained serum testosterone measure-
ment or semen analysis. Measurement of serum LH and FSH levels then helps to determine
whether the hypogonadism is primary (testicular) or secondary (pituitary or hypothalamic).
84. The specific cause of impotence can be diagnosed in 85% of men.
85. The antihypertensive medications that are least likely to cause impotence are angiotensin-converting
enzyme (ACE) inhibitors, angiotensin receptor blockers, and calcium channel blockers.
86. Cysts on ovarian ultrasound do not always signify a diagnosis of polycystic ovary syndrome (PCOS).
87. A serum testosterone level higher than 200 ng/dL or a dehydroepiandrosterone sulfate (DHEAS)
level higher than 1000 ng/mL in a hirsute patient suggests the presence of an androgen-producing
ovarian or adrenal tumor.
88. Primary hypothyroidism can cause amenorrhea, galactorrhea, pituitary enlargement and mildly
elevated serum prolactin levels and thus can mimic a prolactinoma.
89. The common causes of hirsutism are PCOS, CAH, idiopathic or familial hirsutism, and medications.
90. The common causes of virilization are androgen-secreting ovarian or adrenal tumors and CAH.
91. Side effects of anabolic-androgenic steroid abuse include fluid retention, testicular atrophy,
oligospermia, azoospermia, gynecomastia, cholestatic hepatitis, peliosis hepatis, and benign and
malignant hepatic tumors, as well as reduced HDL and higher LDL cholesterol levels.
92. Multiple endocrine neoplasia type 1 (MEN-1), which consists of hyperplasia and/or tumors of the
pituitary gland, pancreatic islets, and parathyroid glands, results from a mutation inactivating the
Menin tumor suppressor gene on chromosome 11.
93. The MEN type 2 (MEN-2) syndromes, which consist of pheochromocytomas and medullary thyroid
carcinoma associated with hyperparathyroidism (MEN-2A) or mucosal neuromas (MEN-2B), result
from mutations in the Ret tumor suppressor gene. Genetic testing for these conditions is now clini-
cally available.
94. Autoimmune polyendocrine syndrome type 1 (APS-1) is a syndrome characterized by hypoparathy-
roidism, adrenal insufficiency, and mucocutaneous candidiasis.
95. APS type 2 (APS-2) consists of adrenal insufficiency, thyroid dysfunction, and diabetes mellitus type 1.
96. Fasting hypoglycemia often produces neuroglycopenic symptoms and is frequently the result of an
organic disorder or surreptitious use of insulin or oral hypoglycemic medications.
97. Insulinomas most often cause fasting hypoglycemia with neuroglycopenic symptoms, but adrener-
gic symptoms and postprandial timing occur in some patients.
98. Most patients with carcinoid syndrome have extensive liver metastases that either impair the meta-
bolic clearance of mediators secreted by the primary tumor or secrete the mediators directly into
the hepatic vein.
99. A carcinoid crisis can be precipitated when a patient with a carcinoid tumor has a superimposed
stress such as infection, surgery, or trauma or is given an adrenergic or sympathomimetic medica-
tion or a monoamine oxidase inhibitor. Carcinoid crisis is best treated with intravenous octreotide
and hydrocortisone.
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100. Mucormycosis is more common during diabetic ketoacidosis because the fungi are thermotolerant,
grow well in an acid pH, grow rapidly in the presence of high glucose, and are one of the few types
of fungi that can use ketones as a food substrate.
101. The most common cause of acanthosis nigricans is diabetes mellitus associated with insulin
resistance and obesity.
102. Aging is associated with losses of muscle mass and bone mass and with increases in fat mass that
may be associated with parallel age-related declines in the production of growth hormone and sex
steroid hormones and increased cortisol secretion.