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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2892_Библиотеки_им_академика_М_И_Перельмана
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bradycardia, nonpitting edema, hair thinning or loss, dry skin, and a diminished
relaxation phase of reflexes.
Laboratory and Imaging Evaluation. In primary hypothyroidism, the TSH level
is elevated, indicating insufficient thyroid hormone production to meet metabolic
demands. Free thyroid levels are low. The pituitary has increased its TSH release in
an attempt to increase the production of thyroid hormones, but the thyroid gland
does not respond. In contrast, patients with secondary hypothyroidism have low
or undetectable TSH levels. Once the diagnosis of primary hypothyroidism is made,
further imaging or serologic testing is unnecessary if the thyroid gland is normal
on physical examination. In cases of secondary hypothyroidism, however, further
testing is needed to determine whether the cause is a hypothalamic or pituitary
problem. This can be done by using a thyrotropin-releasing hormone (TRH) test.
Endogenous TRH is released by the hypothalamus and stimulates the pituitary to
release TSH. When TRH is injected intravenously, a normally functioning pituitary will result in an increase of TSH that can be measured in about 30 minutes.
No increase in TSH after injection of TRH suggests a malfunctioning pituitary
gland. In cases where pituitary dysfunction is suspected, imaging of the pituitary
gland to detect microadenomas and testing of other hormones that are dependent
on pituitary stimulation are indicated.
Treatment
Most healthy, nonpregnant adults with hypothyroidism require about 1.6 µg/kg of
thyroid hormone replacement daily. The recommendation in patients over 50 years
of age is to start with a dose between 25 and 50 µg daily and increase by 25 µg every
3 to 4 weeks until an optimal dose is reached. The same recommendation exists for
those younger than 50 with ischemic heart disease. In pregnancy, thyroid hormone
replacement needs may increase by approximately 30%. This can be met by having the woman take nine doses of her prepregnancy dose of levothyroxine weekly.
A referral to an endocrinologist may also be indicated.
Thyroxine is usually dosed once daily, although some evidence suggests that
weekly dosing may also be effective. In patients with an intact hypothalamicpituitary axis, the adequacy of thyroid replacement can be followed with serial
TSH measurements. Evaluation of TSH levels should be performed 4 to 6 weeks
after an adjustment in medication has been made. If TSH is > 5 mU/L, underreplacement or nonadherence to medication should be suspected. If underreplaced,
increase the levothyroxine dose by 12.5 to 25 µg per day. If TSH < 0.35mU/L,
the patient is being overreplaced, and a daily dose decrease by 25 µg is required.
With increased age, thyroid binding decreases as a consequence of a drop in
serum albumin level, and the medication dosage may need to be reduced by up
to 20%. Annual monitoring of the TSH level in the elderly is necessary to avoid
overreplacement.
Screening. Screening asymptomatic adults for thyroid disorder is controversial.
The US Preventive Services Task Force reports insufficient evidence for or against
routine screening. The American Academy of Family Physicians does not recommend screening in asymptomatic adults. The American Thyroid Association recommends screening all adults age 35 and above every 5 years.
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CLINICAL APPROACH TO NODULAR THYROID DISEASE
Epidemiology
Thyroid nodules are more prevalent in women and increase in frequency with age.
Further workup of identified nodules is indicated, as the incidence of malignancy in
solitary nodules is estimated at 5% to 6%. The incidence of malignancy is higher in
children, adults younger than 30 or older than 60 years, and patients with a history
of head or neck irradiation. Other historical risk factors include a family history of
thyroid cancer, the presence of cervical lymphadenopathy, and the recent development of hoarseness of the voice, progressive dysphagia, or shortness of breath.
Pathophysiology
Thyroid nodules, both solitary and multiple, are common and are often found
incidentally on physical examination, ultrasonography, or computed tomography.
Although their pathogenesis is not clear, nodules are known to be associated with
iodine deficiency, higher gravidity, and the ingestion of goitrogens.
Laboratory Values and Imaging. Initial assessment of thyroid nodules should
include evaluation of thyroid function and ultrasonography to assess for the size of
the nodule. Thyroid function can be assessed by measuring the TSH level. Ultrasonography is the imaging test of choice for assessment of the size of a thyroid
nodule, its characteristics (solid or cystic), the overall size of the thyroid, and the
presence of other nodules that may not have been previously identified.
Functional adenomas that present with hyperthyroidism are rarely malignant.
These represent less than 10% of all nodules. A patient who has a thyroid nodule
and is found to be hyperthyroid should have a radioactive iodine uptake study to
confirm functionality of the nodule.
Nodules measuring greater than 1 cm by ultrasonography in a person with a normal
or elevated TSH require biopsy. This can be done by fine-needle aspiration (FNA),
which is a highly sensitive test. Ultrasound findings suggestive of malignancy
include irregular margins, intranodular vascular spots, and microcalcifications.
Results of the FNA determine further management and treatment. Cytologic evaluation of FNA specimens is reported as nondiagnostic, benign, follicular lesions
of undetermined significance, follicular neoplasms, suspicious for malignancy, or
malignant. Follicular cell malignancy cannot be distinguished cytologically from its
benign equivalent and thus is often read as a follicular lesion of undetermined significance. These patients should be referred to surgery to obtain a definitive evaluation. Papillary, medullary, and anaplastic thyroid carcinomas can be diagnosed
accurately by FNA.
Treatment
Hyperfunctioning nodules are treated with surgery or radioactive ablation therapy, depending on the level of hyperthyroidism. Patients with thyroid malignancy
are treated by thyroidectomy followed by radioactive ablation. These patients will
require long-term follow-up by an endocrinologist.
Thyroid nodules discovered during pregnancy are handled similarly, except
that radioisotope scanning is contraindicated. FNA is safe during pregnancy, and
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thyroidectomy can be performed relatively safely during the second and third trimesters. However, because thyroid cancer is relatively indolent, it may be wise to
defer definitive diagnosis and treatment until the postpartum period in patients
with indeterminate lesions on FNA.
CASE CORRELATION
See also Case 25 (Major Depression and Other Mood Disorders) and
Case 30 (Hypertension).
COMPREHENSION QUESTIONS
15.1 A 28-year-old woman is noted to have had a 10-lb unintended weight gain,
hair loss, dry skin, and fatigue. She is diagnosed with probable hypothyroidism. Which of the following laboratory test results is most consistent with
hypothyroidism?
A. Normal TSH and elevated T4/T3 levels
B. Elevated TSH levels and low T4/T
C. Elevated TSH levels and normal T4/T
D. Low TSH and elevated T4/T3 levels
3
3
15.2 A 35-year-old gravida 2, para 1001 at 11 weeks’ gestation presents with complaint of palpitations, weight loss, nervousness, and tremor. She denies prior
history of thyroid problems. Laboratory studies confirm that TSH is severely
suppressed. Which of the following is the best treatment for this patient at
this time?
A. Propylthiouracil
B. Alpha-adrenergic antagonist
C. Levothyroxine
D. Methimazole
15.3 A 24-year-old woman who is 8 weeks’ pregnant is found to have a thyroid
nodule. A biopsy is performed, and malignancy of the thyroid is diagnosed.
Which of the following management options is most appropriate?
A. Confirm the diagnosis of cancer using radioisotope scanning.
B. Perform an immediate thyroidectomy.
C. Follow clinically until after delivery of child.
D. Treat with radioactive iodine ablation in the second or third trimester.
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15.4 A 28-year-old man presents to his provider for a health maintenance visit.
He feels well and does not report changes in his appetite, weight, energy, or
bowel movements. A firm nodule is palpated in the left lobe of his thyroid.
The nodule is confirmed on ultrasound and measures 0.8 cm and is cystic.
Which of the following is the next step in the workup of this nodule?
A. Radioactive iodine uptake study
B. Fine-needle aspiration
C. Repeat ultrasound in 6 months
D. Referral to surgeon for open biopsy
ANSWERS
15.1 B. Hypothyroidism is marked by low levels of circulating thyroid hormones. In this situation, the usual thyroxine which exerts a negative feedback to TSH is absent; this leads to an increase pituitary secretion of
TSH. Therefore, hypothyroidism presents with an increased TSH and low
serum T3/T4. The other laboratory values (answer A, normal TSH and
elevated T3/T4; answer C, elevated TSH and normal T3/T4; and answer D,
low TSH and elevated T3/T4) are not seen with hypothyroidism.
15.2 A. Experts agree that due to adverse effects of methimazole (answer D) on
fetal development, PTU should be used in the first trimester of pregnancy
and methimazole in the second and third trimesters. Answer B (alphaadrenergic antagonist) is not used for hyperthyroidism, but rather betablocking agents are used to control the tachycardia and tremor and anxiety.
Answer C (levothyroxine) treats hypothyroidism, not hyperthyroidism.
15.3 C. Thyroid cancer detected during pregnancy can usually be observed until
after the pregnancy is complete. If needed, thyroid surgery (answer B) can be
performed safely in the second and third trimesters. The use of radioactive
iodine (answers A and D) is contraindicated in pregnancy.
15.4 C. For thyroid nodules that are < 1 cm, benign appearing, and without the
presence of positive clinical history of thyroid cancers, observation and repeat
thyroid ultrasound in 6 months is appropriate. Thyroid nodules > 1cm
should undergo FNA (answer B), as this is a sensitive and specific test for
thyroid nodules and can help to determine whether it is malignant. Assessment for function (answer A) or referral for surgery (answer D) is not indicated with a small nodule with benign appearances.
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CLINICAL PEARLS
» The most common forms of both hyper- and hypothyroidism are
autoimmune: Graves disease causing hyperthyroidism and Hashimoto thyroiditis causing hypothyroidism.
» The best initial test in assessing thyroid function is a TSH level.
» Once a thyroid nodule is palpated on examination, the first steps are to
obtain a TSH level and a thyroid ultrasound.
» Thyroid disease in pregnancy needs to be evaluated and treated appro-
priately, as both hypothyroidism and hyperthyroidism can have serious
effects on fetal development.
» Thyroid nodules greater than 1 cm in size should be biopsied if the TSH
level is normal or high.
» Approximately 50% of patients with Graves disease also have
exophthalmos.
» Radioactive iodine is the treatment of choice for Graves disease in adult
patients who are not pregnant.
» Thyroid storm is a medical emergency; it is an acute hypermetabolic state
associated with the sudden release of large amounts of thyroid hormone
into circulation.
» Once the diagnosis of primary hypothyroidism is made, further imaging
or serologic testing is unnecessary if the thyroid gland is normal on physical examination.
» Functional adenomas that present with hyperthyroidism are rarely
malignant.
REFERENCES
Baloch ZW, LiVolsi VA, Asa SL, et al. Diagnostic terminology and morphologic criteria for cytologic
diagnosis of thyroid lesions: a synopsis of the National Cancer Institute Thyroid Fine-Needle
Aspiration State of the Science Conference. Diagn Cytopathol. 2008;36:425.
Fitzgerald PA. Endocrine disorders. In: Papadakis MA, McPhee SJ, Rabow MW, eds. Current Medical
Diagnosis & Treatment 2019. New York, NY: McGraw Hill; 2019: Chap. 26. http://accessmedicine.
mhmedical.com/content.aspx?bookid=2449§ionid=194577758. Accessed May 08, 2019.
Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012;
86(3):244-251.
Jameson J, Mandel SJ, Weetman AP. Hypothyroidism. In: Jameson J, Fauci AS, Kasper DL, Hauser
SL, Longo DL, Loscalzo J, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY:
McGraw Hill; 2018: Chap. 376. http://accessmedicine.mhmedical.com/content.aspx?bookid
=2129§ionid=179924583. Accessed May 27, 2019.
Kravets I. Hyperthyroidism: diagnosis and treatment. Am Fam Physician. 2016;93(5):363-370.
CASE 16
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A 74-year-old man comes to your office complaining of trouble sleeping. Further
questioning reveals that he awakens three to four times each night to urinate.
This problem has been noticeably worse over the past year. He has noticed that
he has to strain to initiate voiding, especially in the morning, and that his urine
stream is weak. He complains of “dribbling” at the end of urination, and at times
he is uncertain if he has completely emptied his bladder. He also notes occasional
feelings of urgency and has experienced urinary incontinence twice over the past
month. He denies any fevers, dysuria, hematuria, pain, urethral discharge, or any
changes in his bowel habits. He has a history of prediabetes, hypertension, and
hyperlipidemia; these medical problems are well controlled.
On examination, his temperature is 98.3 °F, blood pressure is 126/78mm Hg,
pulse is 84 beats/min, and respirations are 14 breaths/min. Abdominal examination
is without tenderness, guarding, mass, or organomegaly. There is no suprapubic
fullness or tenderness. On digital rectal examination, his prostate is smooth,
nonnodular, nontender, and moderately enlarged.
▶ What is the most likely diagnosis?
▶ What is the appropriate diagnostic workup?
▶ What is the next step in therapy?
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ANSWERS TO CASE 16:
Male Genitourinary Conditions
Summary: This 74-year-old man presents with
Lower urinary tract symptoms (LUTS)
Nocturia, weak stream and difficulty initiating voiding, sensation of incomplete emp-
tying of his bladder, and urgency
A nontender, nonnodular yet moderately enlarged prostate
Most likely diagnosis: Benign prostatic hyperplasia (BPH).
Diagnostic workup: Measurement of postvoid residual (PVR) volume of urine, uri-
nalysis, serum creatinine, serum prostate-specific antigen (PSA), frequency-volume
chart for evaluation of nocturia.
Next step in therapy: Initial therapy consists of lifestyle modifications, followed
by drug treatment with alpha-1-adrenergic antagonists or 5-alpha-reductase
inhibitors. Incorporating patient preference guides how aggressive therapy for
BPH will be.
ANALYSIS
Objectives
1. Recognize common male genitourinary (GU) conditions. (EPA 1)
2. Know the diagnostic workup and basic management for common male GU
conditions. (EPA 3, 4)
3. Recognize complications associated with common male GU conditions.
(EPA 1, 4, 12)
Considerations
Therapy for BPH is almost entirely symptom driven: A significantly enlarged prostate gland in an asymptomatic patient requires no treatment, while a less enlarged
gland in a patient with severe obstructive symptoms may require surgery. First-line
therapy includes alpha-1-adrenergic antagonists, which reduce sympathetic tone
to the bladder outlet, reducing resistance to flow. The 5-alpha-reductase inhibitors
are slower acting medications that work by reducing the size of the prostate to
relieve urethral obstruction. In cases of obstruction and acute urinary retention,
indwelling catheterization is recommended. Surgical therapy for BPH is second
line and typically undertaken only after a failed trial of medications. Patients with
symptomatic BPH symptoms and/or prostate enlargement should undergo PSA
testing to evaluate for possible prostate cancer.
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APPROACH TO:
Male Genitourinary Conditions
DEFINITIONS
BENIGN PROSTATIC HYPERPLASIA: A histologic diagnosis marked by proliferation of smooth muscle and epithelial cells in the transitional zone of the prostate. Clinically, it presents with LUTS with risk of bladder outlet obstruction.
EPIDIDYMITIS/ORCHITIS: Inflammation of the epididymis and/or testicle,
most commonly due to infectious etiology.
ERECTILE DYSFUNCTION: Consistent or recurrent inability to acquire or sustain an erection of sufficient rigidity and duration for sexual intercourse.
PREHN SIGN: Pain relief with testicular elevation.
CLINICAL APPROACH TO BPH
Epidemiology
The prevalence of LUTS increases as men age; nearly one-half of men experience
moderate-to-severe LUTS by the eighth decade of life. LUTS is also associated
with diabetes, cardiovascular disease, obesity, sedentary lifestyle, and erectile dysfunction (ED). Symptoms of LUTS are measured using the American Urological
Association’s Symptom Index (AUA-SI), which allows response to therapy to be
assessed more objectively.
Pathophysiology
BPH is a pathologic enlargement of the prostate gland that contributes to the
development of LUTS in men. LUTS is a nonspecific term that encompasses all
symptoms related to impaired urine storage or voiding. LUTS can be divided into
obstructive symptoms (eg, hesitancy, straining, weak stream, dribbling) and irritative symptoms (eg, frequency, urgency, nocturia, urge incontinence). Although rare,
untreated BPH can lead to more serious conditions, including acute urinary retention, recurrent urinary tract infections (UTIs), hydronephrosis, and renal failure.
There is no current evidence to support a link between BPH and prostate cancer.
Given its increased prevalence, BPH should be considered in any older male patient
who presents with LUTS, and a digital rectal examination should be performed.
Clinical Presentation
BPH may be asymptomatic, and symptoms do not necessarily correlate with the
degree of prostatic enlargement. Symptoms typically develop slowly and may
progress over a period of years. However, not all patients experience progression
of symptoms; in about one-third of patients, symptoms may improve without
any treatment. LUTS are typically divided into problems with voiding (eg, hesitancy, straining, weak stream, dribbling) and storage (eg, increased frequency,
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urgency, nocturia, urge incontinence). Microscopic or gross hematuria may be
present; gross hematuria warrants additional workup and should not be assumed
to be due to BPH (see Case 14).
Documentation of symptoms is important prior to treatment. The AUA-SI is
a commonly used tool for tracking clinical improvement. The AUA recommends
applying the frequency-volume chart in patients who complain of nocturia, as this
helps guide lifestyle modification therapy.
Differential Diagnosis. The symptoms of BPH can be similar to those caused
by a number of other conditions, including urethral strictures, prostate cancer,
UTI, acute prostatitis, and neurogenic bladder. A careful history and physical
along with a few laboratory tests are helpful to differentiate BPH from these
other diseases.
Urethral strictures should be considered in any patient who has a history of
prior urethral instrumentation or urogenital trauma.
UTI and acute prostatitis typically present with dysuria, urinary frequency, and
occasionally suprapubic or pelvic pain. A urinalysis with significant nitrites
and leukocyte esterase as well as a positive urine culture are indicative of this
diagnosis.
Neurogenic bladder presents with urinary retention and incontinence and is
associated with a history of multiple sclerosis or spinal cord injury.
Bladder cancer should be considered when history includes smoking along
with hematuria.
Anticholinergics, antiemetics, and antihistamines may contribute to LUTS and
can lead to urinary obstruction.
Prostate cancer is generally asymptomatic, although it can cause ureteral
obstruction similar to BPH. Digital rectal examination is useful in differentiating these conditions. BPH typically presents with a smooth, diffusely enlarged
prostate, while prostate cancer may have asymmetry and nodules.
A urinalysis and testing for PSA are recommended by the AUA for the workup
of BPH. Urinalysis is helpful for the detection of blood or an infection. Although a
serum creatinine level is also often obtained, the AUA does not recommend this in
patients for whom there is no suspicion of obstructive nephropathy.
Additional testing may be obtained depending on the patient. Renal and bladder
ultrasonography can rule out obstruction in men with renal dysfunction. Obtaining the PVR urine volume may be helpful before starting an anticholinergic in men
who have suspected neurogenic bladder. A PVR < 200 mL is typically not considered concerning for chronic urinary retention. Finally, urethrocystoscopy can
detect urethral strictures, bladder calculi, and bladder cancer and can provide a
direct visualization of intraurethral prostate enlargement.
Treatment
Treatment of BPH includes conservative management, medical management, and
surgery. The goal of therapy is to improve symptoms and quality of life, as most
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patients do not experience any of the serious complications of BPH. In patients
who have mild, uncomplicated BPH, “watchful waiting” and behavioral modifications alone may be sufficient. Helpful behavioral interventions include reducing
fluid intake prior to bedtime, reducing consumption of weak diuretics such as alcohol and caffeine, and double voiding to empty the bladder more effectively.
Should conservative management fail to improve symptoms, the next step
in treatment is medical management. The mainstay medication classes used in
BPH treatment are alpha-1-adrenergic antagonists (alpha-blockers) and 5-alphareductase inhibitors. It is reasonable to start patients on monotherapy with an
alpha-blocker. Common alpha-blockers include terazosin, doxazosin, tamsulosin,
alfuzosin, and silodosin. These agents are similarly efficacious, although sideeffect profiles vary somewhat. 5-Alpha-reductase inhibitors (eg, finasteride,
dutasteride) can have additional benefit over alpha-blockers in patients with
large prostates because, over time, they cause shrinkage of the prostate. These
medications may take 6 to 12 months to achieve their full effect and are not ideal
as a monotherapy, particularly in a patient who is having moderate-to-severe
BPH symptoms at presentation. Some evidence exists to suggest a lower risk of
development of prostate cancer with use of 5-alpha-reductase inhibitors, while
other evidence suggests an increased risk of development of high-grade prostate
cancer. Surgical management of BPH should generally be reserved for patients
who have failed medical therapy or developed a BPH-related complication such
as acute urinary retention.
CLINICAL APPROACH TO OTHER COMMON
GENITOURINARY DISEASES
Testicular Torsion
Pathophysiology. Testicular torsion is the most serious cause of acute testicular pain
and must be excluded in any patient who presents with acute scrotal pain. It is
caused by twisting of the spermatic cord and its contents, causing ischemia and
potential loss of the affected testicle. The age distribution of testicular torsion is
bimodal, with one peak in the neonatal period and the second peak around puberty.
Torsion is a surgical emergency that requires prompt recognition and treatment
within 6 hours to preserve testicular function.
Clinical Presentation. Patients with testicular torsion typically present with very
sudden onset unilateral scrotal pain of high severity. Nausea and vomiting often
occur. Patients may also have nonspecific symptoms such as fever, urinary frequency, and dysuria. While there are no clear precipitating factors, many patients
describe recent history of trauma or strenuous physical activity. Physical examination may reveal a high-riding testicle with an abnormal horizontal orientation, and
the overlying skin may be indurated, erythematous, and warm. Cremasteric reflex
is absent, as a light stroke to the superior/medial thigh does not elicit the ipsilateral
testicle to move superiorly.
Treatment. In patients with a history and physical examination suggestive of tor-
sion, imaging should not be performed; immediate surgical exploration should occur.
If findings are less clear, ultrasound should be performed. Absent blood flow
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