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Robbins and Cotran Pathology-Endocrine

Terms in this set (66)

A 25-year-old woman has noted breast secretions for the past month. She is not breastfeeding and has never been pregnant. She has not menstruated for the past 5 months. Physical examination yields no abnormal findings. MRI of the brain shows a 0.7-cm mass within the sella turcica. Which of the following additional complications is she most likely to have?
A Acromegaly
B Cushing disease
C Hyperthyroidism
D Infertility
E Neurologic dysfunction
D Infertility
Prolactinomas are more common than other hormone- secreting pituitary adenomas. In addition to her galactorrhea and infertility, this patient also may have decreased libido, and her amenorrhea is secondary to the excessive prolactin secretion. Microadenomas might not have pressure effects on surrounding structures such as optic chiasm, but they can be discovered because of their hormonal effects. Acromegaly results from a growth hormone-secreting pituitary adenoma in an adult. Cushing disease occurs when there is an ACTH- secreting pituitary adenoma. A thyroid-stimulating hormone (TSH)−secreting pituitary adenoma is uncommon, but it could account for elevated levels of T4 and TSH in a hyperthyroid patient. Neurologic dysfunction with hyponatremia from the syndrome of inappropriate diuretic hormone leading to neurologic dysfunction is most often a paraneoplastic syndrome caused by a small cell anaplastic lung carcinoma, but may also be due to head trauma that damages the nerve tracts and neurohypophysis with uncontrolled release of vasopressin (antidiuretic hormone, ADH).
A 20-year-old man's closest friends tell him he looks different now than a year ago, with coarse features. He bought new shoes with his usual size and they do not fit. A year later his 23-year-old brother has similar problems. Both of them have hyperglycemia. Which of the following genetic alterations is most likely present in both brothers?
A Germline mutation of AIP
B Overexpression of cyclin D1
C Fusion of PAX8-PPARG
D Loss of function mutation in PTEN
E Loss of VHL heterozygosity
A Germline mutation of AIP
The aryl hydrocarbon receptor-interacting protein (AIP) gene mutations account for a minority of growth hormone (GH)-producing pituitary adenomas, but may be present in younger persons in familial cases. GH opposes insulin, and excesses can lead to secondary diabetes mellitus. In adults with closed epiphyses, gigantism does not occur, but acromegaly of soft tissues does. Cyclin D1 mutations may be found in some parathyroid adenomas. The PAX8-PPARG fusion gene may be found in some follicular thyroid neoplasms. The tumor suppressor gene PTEN may be mutated in some pancreatic neuroendocrine tumors. The VHL tumor suppressor gene may be associated with some pheochromocytomas.
A 39-year-old woman has had no menstrual periods for the past year, along with malaise, cold intolerance, and loss of body hair. She has had headaches for the past 5 months. On physical examination her lateral visual fields are reduced. She is most likely to have a neoplasm composed of which of the following cell types?
A Beta
B Chief
C Chromaffin
D Chromophobe
E Glomerulosa
F Parafollicular
D Chromophobe
She has a nonfunctioning (null-cell) pituitary adenoma that has enlarged to compress and obliterate the normal adenohypophyseal cells resulting in hypopituitarism; the adenoma also presses on the optic chiasm, producing bitemporal hemianopsia. About a fourth of all pituitary tumors are nonfunctioning. Beta cells of the pancreatic islets of Langerhans produce insulin. Chief cells in the parathyroids produce parathormone that increases serum calcium. Chromaffin cells in the adrenal medulla produce catecholamines. Glomerulosa cells of the adrenal cortex produce corticosteroids. Parafollicular cells (C cells) of the thyroid interstitium produce calcitonin.
A 41-year-old woman notices that her gloves from the previous winter no longer fit her hands. Her facial features have become coarse in the past year, and her voice seems deeper. On physical examination, her blood pressure is 140/90 mm Hg. There is decreased sensation to pinprick over the palms in the distribution of her thumb and first two fingers. A radiograph of the foot shows an increased amount of soft tissue beneath the calcaneus. A chest radiograph shows cardiomegaly. Laboratory studies indicate a fasting serum glucose level of 138 mg/dL and hemoglobin A1c level of 8.6%. Which of the following additional test results is most likely to indicate the cause of her physical and laboratory findings?
A Abnormal glucose tolerance test result
B Failure of growth hormone suppression
C Hyperprolactinemia
D Increased serum TSH level
E Loss of diurnal serum cortisol levels
B Failure of growth hormone suppression
Failure to suppress growth hormone (GH) levels by glucose infusion suggests autonomous GH production. The patient's symptoms suggest acromegaly, and a GH-secreting adenoma is most likely. Acromegaly causes an overall increase in soft tissue in adults because of the anabolic effects of the increase in GH. Because the epiphyses of the long bones are closed in adults, there is not the increase in height, or gigantism, that would be seen in children with a pituitary adenoma that is secreting excessive GH. Instead, the increase in soft tissue mass manifests as increasing shoe or glove size, carpal tunnel syndrome, and coarse facial features. This woman probably has an abnormal glucose tolerance test result, but this does not indicate the underlying cause of diabetes mellitus, which in this case is secondary to acromegaly. A prolactinoma would cause amenorrhea and galactorrhea in a woman. A thyroid-stimulating hormone (TSH)−secreting adenoma of the pituitary can give rise to hyperthyroidism with an increased metabolic rate that would most likely to lead to weight loss, and glucose intolerance is not a feature of hyperthyroidism. Functional pituitary tumors can be detected clinically before they become large enough to cause pressure symptoms such as visual disturbances. Cushing syndrome from an adrenal cortical neoplasm producing cortisol could be accompanied by glucose intolerance, hypertension, and truncal obesity, but there is no overall increase in soft tissues.
A 39-year-old G2, P2 woman, whose last pregnancy was 14 years ago, has had absent menstrual cycles for 6 months. She also reports expression of milk from her breasts. On physical examination, she is normotensive. She is 150 cm tall and weighs 63 kg (body mass index 28). Secondary sex characteristics are normal. Laboratory testing indicates that β-human chorionic gonadotropin level is normal. She has a normal growth hormone stimulation test. CT scan of the head shows no abnormalities of bone and no hemorrhage. Brain MRI shows fluid density within a normal-sized sella turcica. What is the most likely diagnosis?
A Craniopharyngioma
B Empty sella syndrome
C Hereditary hemochromatosis
D Prader-Willi syndrome
E Prolactinoma
F Sheehan syndrome
B Empty sella syndrome
Empty sella syndrome is a rare condition, seen most frequently in obese women, and results from herniation of the arachnoid through the diaphragma sellae. Although the increased pressure can lead to reduction in pituitary tissue through compression atrophy, there is typically adequate functional anterior pituitary to prevent hypopituitarism. This herniation can cause a "stalk section" effect, however, with loss of prolactin inhibition and hyperprolactinemia. A craniopharyngioma is a destructive tumor mass that is usually seen at a younger age. Hemochromatosis can interfere with organ function, including hypopituitarism; onset usually occurs later in women than in men (in the 60s in women compared with the 40s in men), owing to differences in physiologic iron losses (e.g., menstrual blood loss). Prader-Willi syndrome is an example of genomic imprinting with hypothalamic dysfunction seen in prepubertal boys. A prolactinoma could be a microadenoma, but MRI in this case rules this out because of the fluid density in the sella (seen with T2 weighting). If she had Sheehan syndrome after her pregnancy, she would have manifested hypopituitarism within months, not years.
A 21-year-old woman delivers a term infant after an uncomplicated pregnancy. The placenta cannot be delivered, however, and there is substantial hemorrhage, requiring transfusion of 10 U of packed RBCs. She must undergo a hysterectomy. Over the next 3 months, she is unable to pro- duce sufficient milk to breastfeed her infant, and she becomes increasingly fatigued. Laboratory studies show Na+, 134 mmol/L; K+, 5.2 mmol/L; Cl-, 88 mmol/L; CO2, 23 mmol/L; glucose, 59 mg/dL; calcium, 9.3 mg/dL; phosphorus, 3.5 mg/ dL; and creatinine, 0.9 mg/dL. Over the next 5 months, her menstrual cycles do not return. Which of the following laboratory findings is now most likely to be reported in this woman?
A Decreased corticotropin-releasing hormone
B Decreased oxytocin
C Failure of antidiuretic hormone release
D Failure of growth hormone stimulation
E Increased corticotropin
F Increased dopamine
D Failure of growth hormone stimulation
Sheehan syndrome, or postpartum pituitary necrosis, is caused by pituitary enlargement during pregnancy, caus- ing its blood supply to be more tenuous so that intrapartum hypotension with obstetric bleeding complications (e.g., the placenta accreta in this patient) predisposes to infarction. The anterior pituitary is at greater risk than the posterior pituitary. The laboratory findings in this patient suggest ad- renal insufficiency, and her inability to breastfeed is caused by lack of prolactin; loss of menstrual cycles suggests that
follicle-stimulating hormone and luteinizing hormone lev- els are deficient. If she were to have primary adrenal failure, the corticotropin (ACTH) level would be increased, but in her case, ACTH is low because of anterior pituitary failure. Because the hypothalamus is unaffected, corticotropin-re- leasing hormone would still be present. Oxytocin release from the posterior pituitary is probably not affected. She does not have diabetes insipidus from lack of antidiuretic hormone, because the posterior pituitary is less likely to be involved. Dopamine production in the hypothalamus is not affected.
A 42-year-old man has had polyuria and polydipsia for the past 4 months. His medical history shows that he fell off a ladder and hit his head just before the onset of these problems. On physical examination, there are no specific findings. Laboratory findings include serum Na+, 155 mmol/L; K+, 3.9 mmol/L; Cl-, 111 mmol/L; CO2, 27 mmol/L; glucose, 84 mg/ dL; creatinine, 1 mg/dL; and osmolality, 350 mOsm/mL. The urine specific gravity is 1.002. This patient is most likely to have a deficiency of which of the following hormones?
A Corticotropin
B Melatonin
C Oxytocin
D Prolactin
E Vasopressin
E Vasopressin
Diabetes insipidus ensues from lack of antidiuretic hormone (ADH), also called arginine vasopressin. There is failure of resorption of free water in the renal collecting tubules—hence the increased dilute urine with higher serum osmolality and hypernatremia. Corticotropin stimulates the adrenal glands, mainly with the effect of increasing cortisol secretion. Oxytocin is involved in lactation. Prolactin and melatonin deficiencies have no identifiable specific clinical effects in men.
A 69-year-old man has become progressively obtunded over the past week. He has an 80 pack-year history of smoking cigarettes. On physical examination, he is afebrile and normo- tensive. A head CT scan shows no intracerebral hemorrhag- es. Laboratory findings include serum Na+ of 115 mmol/L, K+ of 4.2 mmol/L, Cl- of 85 mmol/L, and bicarbonate of 23 mmol/L. The serum glucose is 80 mg/dL, urea nitrogen is 19 mg/dL, and creatinine is 1.7 mg/dL. Which of the following neoplasms is most likely to be present in this man?
A Adenohypophyseal adenoma
B Adrenocortical carcinoma
C Pheochromocytoma
D Small cell lung carcinoma
E Renal cell carcinoma
D Small cell lung carcinoma
The syndrome of inappropriate antidiuretic hormone (SIADH) secretion results in increased free water resorption by the kidney and subsequent hyponatremia. SIADH is most often a paraneoplastic effect, and small cell (oat cell) ana- plastic carcinoma of the lung (of neuroendocrine derivation and seen almost exclusively in smokers) is the most likely candidate among probable malignant neoplasms. Anterior pituitary adenomas do not produce antidiuretic hormone (ADH), which is released from the posterior pituitary. Ad- renal cortical carcinomas can secrete cortisol or sex steroids, but not ADH. Pheochromocytomas secrete catecholamines. Renal cell carcinomas are known for various paraneoplastic effects, but SIADH is not a high probability.
A 23-year-old man has experienced headaches, polyuria, and visual problems for the past 3 months. On physical examination, he has bilateral temporal visual field deficits. CT scan of the head shows a large, partially calcified, cystic mass occupying the sellar and suprasellar areas. Laboratory findings show a serum prolactin concentration of 60 ng/mL and serum sodium level of 152 mEq/L. Serum calcium, phosphate, and glucose levels are normal. The mass is excised, and histologic examination shows a mixture of squamous epithelial elements and lipid-rich debris containing cholesterol crystals. Which of the following lesions is most consistent with the clinical and laboratory findings in this patient?
A Craniopharyngioma
B Metastases from a lung neoplasm
C Multiple endocrine neoplasia type 1
D Multiple endocrine neoplasia type 2
E Prolactinoma
A Craniopharyngioma
Craniopharyngiomas are uncommon, usually suprasellar neoplasms; they are typically found in young individuals. They are thought to arise from embryologic remnants of the Rathke pouch in the region of the pituitary. These are aggres- sive neoplasms that infiltrate and destroy surrounding tissues, making complete excision difficult. Despite their aggressive behavior, they are composed of benign-appearing squamoid or primitive tooth structures. The increase in prolactin occurs as a "stalk section" effect, and the hypernatremia results from diabetes insipidus caused by destruction of the hypothalamus, posterior pituitary, or both. A metastasis to this location in a young individual is highly unlikely. Multiple endocrine neoplasia (MEN) type 1 includes pituitary adenomas, but not craniopharyngiomas. MEN 2 does not involve the pituitary. Prolactinomas, similar to pituitary adenomas, can enlarge the sella when they are macroadenomas, but are not typically suprasellar or destructive of surrounding structures.
A 42-year-old woman has a sudden onset of fever with headache, nausea, diaphoresis, and palpitations. On physical examination her temperature is 39.2° C; pulse, 115/min; irregular respiratory rate, 30/min; and blood pressure, 150/85 mm Hg. Deep tendon reflexes are 4+ bilaterally. Her outstretched hands exhibit a high frequency tremor. Which of the following drugs should she receive emergently?
A Aspirin
B Hydrocortisone
C Insulin
D Propranolol
E Tetracycline
D Propranolol
Thyroid storm is a medical emergency. There is not enough time to wait for confirmatory laboratory thyroid testing. There are increased catecholamine levels, and the β-blocker propranolol will help prevent emergent death from cardiac failure. Acetaminophen and ice packs are better choices to treat fever alone. Propylthiouracil (PTU) is the antithyroid medication with the fastest onset of action (hours), along with iodine to help reduce pre- formed thyroid hormone output. The fever and ancillary findings here go beyond what would be expected with an acute infection.
A 47-year-old woman has had increasing fatigue with dyspnea and reduced exercise tolerance for the past year. On examination she has non-pitting edema of the lower extremities. Laboratory studies show a serum TSH level of 10 mU/L and T4 level of 2 μg/dL. She is most likely to have pathologic findings affecting which of the following cells?
A Hypophyseal basophils
B Hypophyseal pituicytes
C Hypothalamic glial cells
D Hypothalamic neurons
E Thyroid C cells
F Thyroid follicular cells
F Thyroid follicular cells
The normal feedback loop of peripheral thyroid hormones (T3 and T4) onto the basophils (thyrotrophs) of the adenohypophysis regulates TSH release (under tropic control of TRH from the hypothalamus). When patients with primary thyroid failure, the most common cause for hypothyroidism with myxedema in adults, do not have sufficient residual functioning thyroid follicular cells producing thyroid hormones, then the TSH will rise, as in this case, in conjunction with a low T4 level. The levels of TRH from the hypothalamus are much lower and harder to measure for correlation with thyroid gland function. The measurement of TSH is also the most useful screening test for hyperthyroidism. Neurohypophyseal axons release ADH and oxytocin produced in the hypothalamus, whereas modified glial cells called pituicytes do not release hormones. Thyroid parafollicular, or "C" cells, produce calcitonin.
A 2-year-old child has failure to thrive since infancy. Physical examination shows that the child is short and has coarse facial features, a protruding tongue, and an umbilical hernia. As the child matures, profound intellectual disability becomes apparent. A deficiency of which of the following hormones is most likely to explain these findings?
A Cortisol
B Insulin
C Norepinephrine
D Somatostatin
E Thyroxine (T4)
E Thyroxine (T4)
Cretinism is a condition that is uncommon whenever routine newborn screening is available for testing and treatment at birth for hypothyroidism. Hypothyroidism that develops in older children and adults is known as myxedema. A lack of cortisol from primary adrenal failure leads to Addison disease, or a 21-hydroxylase deficiency could produce congenital adrenal hyperplasia. An absolute deficiency of insulin leads to type 1 diabetes mellitus, but this is more likely to develop in childhood or later, and there would be weight loss. There is no deficiency state caused by a lack of norepinephrine or somatostatin.
A 43-year-old woman has had increasing lethargy and weakness over the past 3 years. She has cold intolerance and wears a sweater in the summer. One year ago, she had menorrhagia, but now she has oligomenorrhea. She has difficulty concentrating, and her memory is poor. She has chronic constipation. On physical examination, her temperature is 35.5° C, pulse is 54/min, respirations are 13/min, and blood pressure is 110/70 mm Hg. She has alopecia, and her skin appears coarse and dry. Her face, hands, and feet appear puffy, with doughlike skin. Laboratory findings show hemoglobin, 13.8 g/dL; hematocrit, 41.5%; glucose, 73 mg/dL; and creatinine, 1.1 mg/dL. The representative microscopic appearance of her causative disease is shown in the figure. Which of the following serologic test findings is most likely to be positive in this woman?
A Anticentromere antibody
B Anti-double-stranded DNA antibody
C Anti-Jo-1 antibody
D Antimitochondrial antibody
E Antiribonucleoprotein antibody
F Anti-thyroid peroxidase antibody
F Anti-thyroid peroxidase antibody
The lymphoid follicles and the large, pink nodules of Hürthle cells in this photomicrograph are typical for Hashimoto thyroiditis. The anti-thyroid peroxidase (antimicrosomal) and antithyroglobulin antibody titers typically are in- creased in patients with Hashimoto thyroiditis when thyroid enlargement is still present. In the later, "burnt-out" phase of Hashimoto thyroiditis, the antibodies are sometimes undetectable—only the hypothyroidism is. The thyroid-stimulating hormone (TSH) level is an indication of whether there is a primary disease in the thyroid. If the patient appears hypothyroid and a primary thyroid disease (e.g., Hashimoto thyroiditis) is suspected, the TSH level is elevated. If the patient appears hyperthyroid and a primary thyroid disease (e.g., Graves disease) is suspected, the TSH level is decreased. Anticentromere antibody is characteristic of limited scleroderma (CREST syndrome). Anti-double-stranded DNA antibody is very specific for systemic lupus erythematosus. Anti-Jo-1 antibody can be seen in polymyositis. Increased antimitochondrial antibody indicates primary biliary cirrhosis. Antiribonucleoprotein antibodies are seen in some collagen vascular diseases, such as mixed connective tissue disease.
A 37-year-old woman has had difficulty swallowing and a feeling of fullness in the anterior neck for the past week. She is recovering from a mild upper respiratory tract infection 1 month ago. On physical examination, her temperature is 37.4° C, pulse is 74/min, respirations are 16/min, and blood pressure is 122/80 mm Hg. Palpation of her diffusely enlarged thyroid elicits pain. Laboratory studies show an increased serum T4 level and a decreased TSH level. Two months later, she no longer has these complaints. The T4 level is now normal. Which of the following conditions is most likely to have produced these findings?
A Hashimoto thyroiditis
B Medullary thyroid carcinoma
C Subacute granulomatous thyroiditis
D Toxic follicular adenoma
E Toxic multinodular goiter
C Subacute granulomatous thyroiditis
Subacute granulomatous thyroiditis (de Quervain thyroiditis) is a self-limited condition that can be of viral origin because many cases are preceded by an upper respiratory infection. The transient hyperthyroidism results from inflammatory destruction of the thyroid follicles and release of thyroid hormone. The released colloid acts as a foreign body, producing florid granulomatous inflammation in the thyroid. Hashimoto thyroiditis can enlarge the thyroid transiently, but there is usually no pain or hyperthyroidism. Thyroid neoplasms are not typically associated with signs and symptoms of inflammation and are rarely functional. A toxic multinodular goiter likewise produces no signs of inflammation, and does not reverse functionality.
A 30-year-old woman has given birth to her second child. She develops heat intolerance and loses more weight than expected postpartum. On physical examination, her thyroid gland is enlarged but painless; there are no other remarkable findings. Laboratory studies show a serum T4 level of 12 μg/dL and a TSH level of 0.4 mU/L. A year later she is euthyroid. Which of the following is most indicative of the pathogenesis of this patient's disease?
A Activational mutations in the RET proto-oncogene
B Anti-thyroid peroxidase antibodies
C Irradiation of the neck during childhood
D Prolonged iodine deficiency
E Recent viral upper respiratory tract infection
B Anti-thyroid peroxidase antibodies
The presence of autoantibodies in the serum in this patient with transient hyperthyroidism would suggest Hashimoto thyroiditis ("hashitoxicosis"), but the variant called subacute lymphocytic painless thyroiditis may affect 1 in 20 postpartum women, and a minority progress to hypothyroidism. Mutations in the RET proto-oncogene are associated with papillary carcinoma and medullary carcinoma of the thyroid. Irradiation of the thyroid gland can give rise to hypothyroidism, but it is unlikely that irradiation in childhood would give rise to hypothyroidism at age 60 years. Irradiation also can predispose to the development of papillary carcinoma, but these tumors usually do not affect thyroid hormone secretion. An iodine deficiency can lead to hypothyroidism, but a goiter would be present. A history of a viral infection sometimes precedes subacute granulomatous thyroiditis, which is typically a self-limited disease that lasts for weeks to 2 months.
A 20-year-old woman and her twin sister both experience increasing diplopia. Their conditions develop within 3 years of each other. On physical examination, they have exophthalmos and weak extraocular muscle movement. The thyroid gland is diffusely enlarged but painless in each sister, and there is no lymphadenopathy in either woman. Which of the following serum laboratory findings is most likely to be reported in these sisters?
A Decreased free thyroxine level
B Decreased thyroid-stimulating hormone level
C High titer thyroid peroxidase autoantibodies
D Increased thyrotropin-releasing hormone level
E Increased triiodothyronine level
B Decreased thyroid-stimulating hormone level
Exophthalmos is a feature seen in about 40% of individuals with Graves disease. The hyperfunctioning thyroid gland leads to an increased T4 level, with positive feedback from the pituitary to decrease thyroid-stimulating hormone (TSH) secretion. There is about 50% concordance of Graves disease among identical twins. The autoimmune character of this disorder is evidenced by an association with HLA-DR3 and by the presence of an autoantibody against TSH receptor that activates T4 secretion. An increased thyrotropin-releasing hormone (TRH) level would increase the TSH level and increase the T4, but feedback typically occurs at the level of the pituitary and the hypothalamus, and abnormal increases in TRH are uncommon. Anti-thyroid peroxidase antibodies can be seen in Hashimoto thyroiditis and in Graves disease, but the highest titers occur in Hashimoto thyroiditis. T3 levels are less likely to be elevated than T4 levels.
A 21-year-old woman has noted increasing fatigue and a 7-kg weight loss without dieting over the past 4 months. She also has increasing anxiety and nervousness with diarrhea. Physical examination shows a diffusely enlarged thyroid gland. Her temperature is 37.5° C, pulse is 103/min, respirations are 28/min, and blood pressure is 140/75 mmHg. A radionuclide scan of the thyroid shows a diffuse increase in uptake. The figure shows the representative microscopic ap- pearance of the thyroid gland. What is most likely to produce these findings?
A Antibodies against TSH receptor
B Dietary deficiency of iodine
C Irradiation of the neck
D Maternal deficiency in T4
E Mutation in the RET proto-oncogene
A Antibodies against TSH receptor
The tall columnar epithelium with papillary infoldings and scalloping of the colloid is characteristic of Graves disease, which leads to hyperthyroidism. This disease is caused by autoantibodies that bind to the thyroid-stimulating hormone (TSH) receptor and mimic the action of TSH. Dietary iodine deficiency can cause diffuse compensatory enlargement of thyroid, but it does not cause hyperthyroidism. Irradiation of the neck is a predisposing factor for papillary carcinoma of the thyroid. Maternal thyroid hormone deficiency may affect childhood mental development. Mutations in the RET proto-oncogene occur in papillary carcinoma of the thyroid and in medullary carcinomas of the thyroid. These neoplasms do not cause diffuse enlargement of the gland, hyperthyroidism, or diffuse increase in radioiodine uptake. Tumors usually produce "cold nodules" on radioiodine scans.
A 40-year-old man notes weight loss, increased appetite, and double vision for 6 months. On physical examination, his temperature is 37.7° C, pulse is 106/min, respirations are 20/min, and blood pressure is 140/80 mm Hg. A fine tremor is observed in his outstretched hands. He has bilateral proptosis and corneal ulceration. Laboratory findings include a serum TSH level of 0.1 mU/L. A radioiodine scan indicates increased diffuse uptake throughout the thyroid. He receives propylthiouracil therapy, and his condition improves. Which of the following best describes the microscopic appearance of his thyroid gland before therapy?
A Destruction of follicles, lymphoid aggregates, and Hürthle cell metaplasia
B Enlarged thyroid follicles lined by flattened epithelial cells
C Follicular destruction with inflammatory infiltrates containing giant cells
D Nodules with nests of cells separated by hyaline stroma that stains with Congo red
E Papillary projections in thyroid follicles and lymphoid aggregates in the stroma
E Papillary projections in thyroid follicles and lymphoid aggregates in the stroma
The clinical findings in this case point to hyperthyroidism, and the increased, diffuse uptake corroborates Graves disease as a probable cause because the thyroid- stimulating hormone (TSH) level is quite low. The thyroid- stimulating immunoglobulins that appear in this autoim- mune condition result in diffuse thyroid enlargement and hyperfunction, and papillary projections lined by tall co- lumnar epithelial cells. Destruction of thyroid follicles with lymphoid aggregates and Hürthle cell metaplasia is characteristic of Hashimoto thyroiditis. A goiter has enlarged follicles and flattened epithelial cells; most of these patients are euthyroid. Follicular destruction and the presence of giant cells occur in granulomatous thyroiditis. Nests of cells in a Congo red-positive hyaline stroma characterize a medullary carcinoma, which can be multifocal, but is not diffuse and does not lead to hyperthyroidism.
A 45-year-old woman from Kathmandu, Nepal, reports a feeling of fullness in her neck, but has no other concerns. The enlargement has been gradual and painless for more than 1 year. Physical examination confirms diffuse enlargement of the thyroid gland without any apparent masses or lymphade- nopathy. Laboratory studies of thyroid function show a nor- mal free T4 level and a slightly increased TSH level. What is the most likely cause of these findings?
A Diffuse nontoxic goiter
B Follicular adenoma
C Hashimoto thyroiditis
D Papillary carcinoma
E Subacute granulomatous thyroiditis
F Toxic multinodular goiter
A Diffuse nontoxic goiter
Diffuse nontoxic goiter is most often caused by dietary iodine deficiency. This condition is endemic in regions of the world where there is a deficiency of iodine (e.g., inland mountainous areas); it also may occur sporadically. As in this case, patients are typically euthyroid. A follicular adenoma rarely functions to produce excess thyroid hormone; most are "cold," nonfunctioning nodules that do not involve the thyroid diffusely. A chronic lymphocytic thyroiditis, such as Hashimoto thyroiditis, initially can produce thyroid enlargement, but atrophy eventually occurs with resulting hypothyroidism. Papillary carcinomas most often produce a mass effect or metastases and do not affect thyroid func- tion. Subacute granulomatous thyroiditis can lead to diffuse enlargement, and transient hyperthyroidism can occur, but the disease typically runs a course of no more than 6 to 8 weeks. Plummer disease, or toxic multinodular goiter, occurs when there is a hyperfunctioning nodule in a goiter.
A 14-year-old girl noticed gradual neck enlargement during the past 8 months. On physical examination her thyroid gland is diffusely enlarged. Her serum TSH level is normal. A dietary history is most likely to reveal that she has begun eating more of which of the following foods?
A Cabbage
B Fava beans
C Fish
D Plantains
E Rye bread
A Cabbage
She has developed a sporadic goiter. Vegetables of the Brassicaceae family, including cabbage, turnips, and Brussels sprouts, contain glucosinolate, which can decompose to release thiocyanate, a by product that interferes with thyroid hormone synthesis. Thus such substances are known as goitrogens. Young persons with increased demand for thyroid hormone are at increased risk. Fava beans contain oxidizing agents that incite hemolysis in persons with glucose- 6-phosphate dehydrogenase (G6PD) deficiency. In addition, beans contain long-chain sugars that are indigestible with human intestinal enzymes, leaving them to be fermented by colonic bacteria that release gas (flatus). Fish have omega-3 fatty acids that protect against atherogenesis. Plantains are starchy, as anyone mistaking them for sweet bananas soon discovers; rare food allergy develops to them. Fungus growing on moldy rye produces ergot poisoning.
A 70-year-old man has had greater difficulty swallowing for the past 2 years. Over the past 6 months, he has lost 3 kg. On physical examination, his temperature is 37.3° C, and pulse is 102/min. There is fullness to the anterior neck, with a 5 × 10 cm irregular mass on palpation. Laboratory studies show serum TSH of 0.2 mU/L. A thyroid scintigraphic scan shows a 1.5-cm nodule with increased uptake in the right thyroid lobe, and decreased uptake into the remaining enlarged thyroid. What is the most likely diagnosis?
A Follicular adenoma
B Graves disease
C Hashimoto thyroiditis
D Papillary carcinoma
E Toxic multinodular goiter
E Toxic multinodular goiter
A long-standing diffuse goiter can evolve into a multinodular goiter, and one of the nodules can begin hyper- functioning to cause so-called Plummer disease. This "toxic" nodule has acquired growth and functional characteristics similar to a benign neoplasm, such as a follicular adenoma, but one that is functional. Rare toxic follicular adenomas can function and produce "hot" nodules, but the remaining gland is often atrophic, not enlarged. In Graves disease, the thyroid is enlarged, but usually diffusely, without pronounced nodularity, so that there is increased uptake into the entire gland. In addition, clinical features such as dermopathy and ophthalmopathy that are lacking with Plummer disease are associated with Graves disease. There may be initial diffuse thyroid enlargement with Hashimoto thyroiditis and tran- sient hyperfunction, but over time the thyroid atrophies, and hypothyroidism ensues. It is extremely rare for a papillary carcinoma to function, and although this would be a hot nodule, the remaining thyroid would not be enlarged.
A 38-year-old woman felt a small bump on the right side of her neck 1 month ago, and it has not changed since then. Physical examination shows a 1-cm painless nodule palpable in the right lower pole of the thyroid gland. There is no lymphadenopathy. Radionuclide scanning shows that the nodule does not absorb radioactive iodine, and no other nodules are present. A fine-needle aspiration biopsy of the nodule is done, and the cytologic features are those of a follicular neoplasm. Which of the following laboratory findings is most likely to be present in this patient?
A Anti-TSH receptor immunoglobulins
B High free T4
C Low T3
D Normal TSH
E Anti-thyroid peroxidase antibodies
D Normal TSH
Solitary "cold" and solid (not cystic) thyroid nodules are likely to be neoplastic, and most are benign follicular ad- enomas that do not affect thyroid function. If the nodule was hyperfunctioning, and produced hyperthyroidism, it would appear "hot" on the scan, and suppress thyroid-stimulating hormone (TSH). Anti-TSH receptor immunoglobulins can be seen in Graves disease, as may high T4 and low TSH levels, but this is a diffuse disease of the thyroid. T3 levels are rarely measured. Antimicrosomal and antithyroglobulin antibodies are seen in Hashimoto thyroiditis (and Graves disease), but thyroiditis is a diffuse process and unlikely to produce a solitary nodule. As Hashimoto thyroiditis progresses, decreasing function of the thyroid can lead to decreasing T4 level and increasing TSH level, typical of primary thyroid failure.
A 30-year-old woman has a 6-month history of weight loss (3 kg), hand tremors, mild watery diarrhea, and heat intolerance. On physical examination, vital signs are temperature, 37.3° C; pulse, 103/min with sinus rhythm; respirations, 20/ min; and blood pressure, 125/85 mm Hg. She has a 1-cm firm, painless nodule palpable on the left side of her neck. There is no lymphadenopathy. No other abnormal findings are noted. Laboratory findings include a total serum T4 of 11.6 μg/dL with TSH of 0.2 mU/L. A scintigraphic scan shows more uptake of radioactive iodine into the nodule than the surrounding thyroid. A partial thyroidectomy is performed, and microscopic examination of the excised nodule shows well- differentiated thyroid follicles without vascular or capsular invasion. Molecular analysis of this nodule is most likely to reveal which of the following genetic changes?
A Activating missense mutation of GNAS1 gene
B Fusion gene formed by PAX8 and PPARG genes
C Gain of function mutation of TSH receptor gene
D Mutational activation of RET tyrosine kinase receptor
E Overexpression of cyclin D1 (CCND1) gene
F Stop codon mutation of autoimmune receptor (AIRE) gene
C Gain of function mutation of TSH receptor gene
A thyroid nodule that is well differentiated, noninvasive, and hyperfunctioning suggests a "toxic" follicular adenoma, and a large proportion of these adenomas have activating mutations of the thyroid-stimulating hormone (TSH) receptor-signaling pathway involving the TSH receptor or associated G protein. Mutation of the GNAS1 gene is seen in McCune-Albright syndrome and some pituitary adenomas. A PAX8-PPARG fusion gene is found in certain follicular carcinomas of the thyroid. Activation of the RET gene occurs in papillary thyroid carcinomas. Overexpression of the cyclin D1 gene (CCND1) is characteristic of parathyroid adenomas. The AIRE gene regulates expression of self-antigens in the thymus, and mutation in this gene causes autoim- mune polyendocrinopathy affecting adrenals, parathyroids, gonads, and gastric parietal cells with destruction of these tissues and consequent hypofunction.
A 44-year-old, otherwise healthy woman feels a small lump on the left side of her neck. A firm, painless, 1.5-cm cervical lymph node is palpable. The thyroid gland is not en- larged. A chest radiograph is unremarkable. Laboratory find- ings include serum glucose, 83 mg/dL; creatinine, 1.2 mg/ dL; calcium, 9.1 mg/dL; phosphorus, 3.3 mg/dL; thyroxine, 8.7 μg/dL; and TSH, 2.3 mU/L. The hemoglobin is 14 g/dL, platelet count is 240,400/mm3, and WBC count is 5830/mm3. A fine-needle aspiration biopsy of the thyroid gland is done. What is the most likely diagnosis?
A Anaplastic carcinoma
B Follicular carcinoma
C Medullary carcinoma
D Papillary carcinoma
E Parathyroid carcinoma
F Small lymphocytic lymphoma
D Papillary carcinoma
Papillary thyroid carcinomas may present initially with metastases, and local lymph nodes are the most common sites for metastases. The primary site may not be detect- able as a palpable nodule. Papillary carcinoma is the most common thyroid malignancy. Metastases to the thyroid are uncommon. Anaplastic carcinomas are uncommon, but are very aggressive, locally invasive lesions. Follicular and medullary carcinomas tend to spread hematogenously. A parathyroid carcinoma is a locally infiltrative mass, and the serum calcium level is usually quite high in such patients. A small lymphocytic lymphoma, which is the tissue form of chronic lymphocytic leukemia, is uncommon at this patient's age, usually involves multiple nodes, and is accompanied by an elevated WBC count.
A 45-year-old man has felt a lump on the left side of his neck for 4 months. Physical examination shows a nontender nodule on the left lobe of the thyroid gland. An adjacent cervical lymph node is enlarged and nontender. Laboratory studies show no thyroid autoantibodies in his serum, and the T4 and TSH levels are normal. A thyroidectomy is performed; the figure shows the microscopic appearance of the nodule. Which of the following etiologic factors is most likely to be involved in the pathogenesis of the thyroid nodule in this patient?
A Autoimmunity
B Chronic dietary iodine deficiency
C Consumption of goitrogens
D RET gene mutation
E Viral infection
...
A 62-year-old woman has felt a lump on the right side of her neck for 5 months. On physical examination, she has no palpable lymphadenopathy. A fine-needle aspiration biopsy is done, and she undergoes a thyroidectomy. A 3-cm solid mass within the right thyroid lobe has the microscopic appearance shown in the figure. Six months later, she has pain in the right thigh. A radiograph shows a fracture of the right femur in an area of lytic bone destruction. A radioiodine scan shows uptake localized to the region of the fracture. Which of the following is the most likely diagnosis?
A Papillary carcinoma
B Follicular carcinoma
C Granulomatous thyroiditis
D Hashimoto thyroiditis
E Non-Hodgkin lymphoma
...
A 44-year-old man with no previous illnesses has been bothered by progressive hoarseness, shortness of breath, and stridor for the past 3 weeks. On physical examination, he has a firm, large, tender mass involving the entire right thyroid lobe. CT scan shows extension of this mass posterior to the trachea and into the upper mediastinum. A fine-needle aspiration biopsy of the mass is done, and microscopically shows pleomorphic spindle cells. The mass is noted at surgery to have infiltrated the adjacent skeletal muscle. Four of seven cervical lymph nodes have metastases. Pulmonary metastases also are identified on a chest radiograph. Which of the following neoplasms is most likely to be present in this man?
A Anaplastic carcinoma
B Follicular carcinoma
C Medullary carcinoma
D Non-Hodgkin lymphoma
E Papillary carcinoma
...
A 42-year-old woman has noted increasing fullness in her neck for the past 7 months. On physical examination, her thyroid gland is diffusely and asymmetrically enlarged and nodular. There is no lymphadenopathy. She undergoes thyroidectomy. Gross examination of the thyroid shows a multicentric thyroid neoplasm; microscopically, the neoplasm is composed of polygonal- to spindle-shaped cells forming nests and trabeculae. There is a prominent, pink hyaline stroma that stains positively with Congo red. Electron microscopy shows varying numbers of intracytoplasmic, membrane-bound, electron-dense granules. Immunohistochemical staining for which of the following antigens is most useful for diagnosis of this neoplasm?
A Calcitonin
B CD3
C Cytokeratin
D Estrogen receptor
E Parathyroid hormone
F Vimentin
...
A 40-year-old man experiences weakness and easy fatigability of 2 months' duration. Physical examination yields no remarkable findings. Laboratory studies show serum calcium of 11.5 mg/dL, inorganic phosphorus of 2.1 mg/dL, and serum parathyroid hormone of 58 pg/mL, which is near the top of the reference range. A radionuclide bone scan fails to show any areas of increased uptake. What is the most likely cause of these findings?
A Chronic renal failure
B Hypervitaminosis D
C Medullary thyroid carcinoma
D Parathyroid adenoma
E Parathyroid carcinoma
F Parathyroid hyperplasia
...
A 63-year-old woman had frequent headaches for 1 month. She now suddenly experiences a generalized seizure and becomes obtunded. She is taken to the emergency department, where a physical examination reveals an irregular heart rate. Laboratory findings include serum calcium of 15.4 mg/ dL, serum phosphorus of 1.9 mg/dL, and albumin of 4.2 g/ dL. A chest radiograph shows multiple lung masses and lytic lesions of the vertebral column. Which of the following conditions best accounts for these findings?
A Chronic renal failure
B Disseminated tuberculosis
C Metastatic breast carcinoma
D Parathyroid carcinoma
E Vitamin D toxicity
...
A 40-year-old woman notes lethargy, weakness, and constipation for the past 6 months. On physical examination, she is afebrile and normotensive, and her heart rate is irregular. There is pain on palpation of the left third proximal finger. An ECG shows a prolonged QT (corrected) interval. Laboratory studies show glucose, 73 mg/dL; creatinine, 1.2 mg/dL; calcium, 11.6 mg/dL; phosphorus, 2.1 mg/dL; total protein, 7.1 g/dL; albumin, 5.3 g/dL; and alkaline phosphatase, 202 U/L. A radiograph of the left hand shows focal expansion by a cystic lesion of the third proximal phalanx. A technicium radionuclide scan shows a 1-cm area of increased uptake in the right lateral neck. A mutation in which of the following genes is most likely present in this woman?
A GNAS1
B MEN1
C TP53
D RET
E VHL
...
A 68-year-old man has experienced increasing malaise for 3 years. Physical examination shows no remarkable findings. Laboratory findings include a serum creatinine level of 4.9 mg/dL and urea nitrogen level of 45 mg/dL. Abdominal CT scan shows small kidneys. Which of the following endocrine glandular lesions has developed secondary to the underlying disease in this patient?
A Adrenal atrophy
B Islet cell hyperplasia
C Multinodular goiter
D Parathyroid hyperplasia
E Pituitary microadenoma
...
A 47-year-old woman noticed a lump in her neck 1 week ago. On physical examination, there is a 2-cm nodule in the right lobe of the thyroid gland. A fine-needle aspiration biopsy is performed, and microscopic examination of the specimen shows cells consistent with a follicular neoplasm. She undergoes a subtotal thyroidectomy. Which of the following laboratory tests should be performed on this patient in the immediate postoperative period?
A Antithyroglobulin antibody
B Calcitonin
C Calcium
D Parathyroid hormone
E TSH
...
A 27-year-old man has controlled his diabetes mellitus for the past 10 years with insulin injections. This morning, his roommate is unable to awaken him. The man is unconscious when brought to the emergency department. On physical examination, his temperature is 37° C, pulse is 91/min, res- pirations are 30/min, and blood pressure is 90/65 mm Hg. Laboratory findings include a high plasma level of insulin and a lack of detectable C peptide. Urinalysis shows no blood, protein, or glucose, but 4+ ketonuria. Which of the following conditions is most likely to be present?
A Acute myocardial infarction B Bacteremia
C Hepatic failure
D Hyperosmolar syndrome
E Hypoglycemic coma
F Ketoacidosis
...
Blood relatives of individuals diagnosed with type 1 or type 2 diabetes mellitus are studied for 10 years. Laboratory testing for glucose and insulin levels and autoantibody formation is performed on a periodic basis. The HLA types of the subjects are determined. A cohort of the subjects who are 8 to 22 years old has no overt clinical illnesses and no hyperglycemia; however, autoantibodies to glutamic acid decarboxylase are present. Many subjects in this cohort have the HLA-DR3 and HLA-DR4 alleles. Which of the following pancreatic abnormalities is most likely to be found in this cohort of study subjects?
A Acinar acute inflammation and necrosis
B Acinar fibrosis and fatty replacement
C Islet amyloid deposition
D Islet hyperplasia
E Insulitis
F Normal islets in a fibrous stroma
...
A 23-year-old woman has a routine health status examination. Her body mass index is 22. Laboratory studies show fasting plasma glucose is 130 mg/dL. Urinalysis shows mild glucosuria, but no ketonuria or proteinuria. She has no detectable insulin autoantibodies. Her father was similarly affected at age 20 years. She is most likely to have a mutation in a gene encoding for which of the following?
A Glucagon
B Glucokinase
C GLUT4
D Insulin
E MHC DR
...
A 13-year-old girl collapses while playing basketball. On arrival at the emergency department, she is obtunded. On physical examination, she is hypotensive and tachycardic with deep, rapid, labored respirations. Laboratory studies show serum Na+, 151 mmol/L; K+, 4.6 mmol/L; Cl-, 98 mmol/L; CO2, 7 mmol/L; and glucose, 521 mg/dL. Urinalysis shows 4+ glucosuria and 4+ ketonuria levels, but no protein, blood, or nitrite. Which pathologic abnormality is most likely to be present in her pancreas at the time of her collapse?
A Loss of islet beta cells
B Acute inflammation of islets
C Amyloid replacement of islet beta cells
D Chronic inflammation of islets
E Hyperplasia of alpha cells
F Pancreatic neuroendocrine tumor
...
A study of patients more than 25 years of age with body mass index above 30, dyslipidemia, hypertension, and fasting glucose averaging 115 mg/dL is performed. They have adipose tissue abnormalities including increased nonesterified fatty acid release, altered adipokines with decreased adiponectin, greater proinflammatory cytokine release, and diminished peroxisome proliferator-activated receptor gamma (PPARγ) function. Which of the following is the best initial therapeutic intervention for these patients?
A Adrenalectomy
B Caloric restriction
C Insulin injection
D l-Thyroxine
E Liposuction
...
An infant is born following premature delivery. Multiple external congenital anomalies are noted. The infant exhibits a seizure soon after birth. The blood glucose is 19 mg/dL. Which of the following maternal diseases is the most likely cause for the observed findings in this infant?
A Cystic fibrosis
B Diabetes mellitus, type 2
C Gestational diabetes
D Maturity onset diabetes of the young
E Pancreatic neuroendocrine tumor
...
A clinical study is conducted in patients diagnosed with either type 1 or type 2 diabetes mellitus. Persons with either type develop complications of accelerated and advanced atherosclerosis. All untreated patients have an elevated hemoglobin A1c. Which of the following features common to patients with either type 1 or type 2 diabetes mellitus is most likely to be found by this study?
A Association with certain MHC class II alleles
B High concordance rate in monozygotic twins
C Marked resistance to the action of insulin
D Nonenzymatic glycosylation of proteins
E Presence of islet cell antibodies
...
A 50-year-old man with fasting blood glucose >140 mg/dL on two occasions is put on a restricted caloric diet and started on a glucagon-like peptide-1 (GLP-1) receptor agonist. Which of the following laboratory studies is most likely to afford the best method of monitoring disease control in this man?
A Cholesterol, total
B Fasting plasma glucose
C Glycosylated hemoglobin
D Microalbuminuria
E Random plasma glucose
F Serum fructosamine
...
A 50-year-old man has had a nonhealing ulcer on the bottom of his foot for 2 months. On examination, the 2-cm ulcer overlies the right first metatarsal head. There is reduced sensation to pinprick in his feet. His visual acuity is reduced bilaterally. Laboratory studies show serum creatinine is 2.9 mg/dL. Which of the following laboratory test findings is he most likely to have?
A Glucosuria
B Hypoalbuminemia
C Hypokalemia
D Leukopenia
E Steatorrhea
F Uricosuria
...
A 52-year-old man has been concerned about a gradual weight gain over the past 30 years. He is 174 cm (5 feet 7 inch- es) tall and weighs 91 kg (body mass index 30). He is taking no medications. On physical examination, he has decreased sensation to pinprick and light touch over the lower extremities. Patellar reflexes are reduced. Motor strength seems to be normal in all extremities. Laboratory studies show blood glucose of 169 mg/dL, creatinine of 1.9 mg/dL, total cholesterol of 220 mg/dL, HDL cholesterol of 27 mg/dL, and triglycerides of 261 mg/dL. A chest radiograph shows mild cardiomegaly. Five years later, he has claudication in the lower extremities when he exercises. Based on these findings, which of the following complications is most likely to occur in this man?
A Gangrene
B Hypoglycemic coma
C Ketoacidosis
D Mucormycosis
E Pancreatitis
F Systemic amyloidosis
...
A 45-year-old woman has had angina pectoris, polyuria, and polydipsia for the past 5 years. On physical examination, she has a body mass index of 32. Laboratory studies show her hemoglobin A1c is 10%. Urinalysis shows proteinuria, but no ketonuria. The representative microscopic appearance of her kidneys is shown in the figure. Which of the following is the most likely mechanism leading to the disease causing her findings?
A Chronic pancreatitis
B Glucokinase gene mutation
C Insulin resistance
D Systemic amyloidosis
E T-cell mediated B-cell destruction
...
A 50-year-old man has a 35-year history of diabetes mellitus. During this time, he has had hemoglobin A1c values between 7% and 10%. He now has problems with sexual function, including difficulty attaining an erection. He also is plagued by mild but recurrent low-volume diarrhea and difficulty with urination. He has delayed gastric emptying. These problems are most likely to originate from which of the following mechanisms of cellular injury?
A Cross-linking of extracellular matrix proteins
B Production of vascular endothelial growth factor
C Abnormal transforming growth factor-beta signaling
D Increased endothelial procoagulant activity
E Nonenzymatic glycosylation
F Polyol-induced susceptibility to oxidative stress
...
A 74-year-old woman is admitted to the hospital in an obtunded condition. Her temperature is 37° C, pulse is 95/ min, respirations are 22/min, and blood pressure is 90/60 mm Hg. She appears dehydrated and has poor skin turgor. Her serum glucose level is 872 mg/dL. Urinalysis shows 4+ glucosuria, but no ketones, protein, or blood. Which of the following factors is most important in the pathogenesis of this patient's condition?
A Autoimmune insulitis
B Glucokinase gene mutation
C HLA-DR3/HLA-DR4 genotype
D Peripheral insulin resistance
E Virus-induced injury to beta cells in islets
...
A 40-year-old woman has experienced chest pain on exertion for the past 2 months. A month ago, she had pneumonia with Streptococcus pneumoniae cultured from her sputum. On physical examination, she has a body mass index of 35. A random blood glucose value is 132 mg/dL. The next day, a fasting blood glucose is 120 mg/dL, followed by a value of 122 mg/ dL on the following day. She is given an oral glucose tolerance test, and her blood glucose is 240 mg/dL 2 hours after receiving the standard 75-g glucose dose. On the basis of these findings, she is prescribed an oral thiazolidinedione (TZD) drug. After 2 months of therapy, her fasting blood glucose is 90 mg/ dL. The beneficial effect of TZD in this patient is most likely related to which of the following processes?
A Activation of PPARγ nuclear receptor in adipocytes
B Decreased production of insulin autoantibodies
C Greater density of insulin receptors in adipocytes
D Increased half-life of circulating plasma insulin
E Reduced secretion of glucagon by a cell in islets of Langerhans
F Regeneration of beta cells in islets of Langerhans
...
A family is followed longitudinally for two generations. Four of eight children develop hyperglycemia by age 18 years. They are found to have serum islet autoantibodies. They have similar MHC I and MHC II loci. Treatment with insulin injections normalizes their Hgb A1c levels. Which of the following is the most likely mechanism leading to their disease?
A Chloride ion channel abnormality
B Chromosome 21 trisomy
C Glucokinase gene mutation
D Peripheral insulin resistance
E Loss of T-cell tolerance
...
A 33-year-old woman has had several "fainting spells" over the past 6 months. Each time, she has a prodrome of light- headedness followed by a brief loss of consciousness. After each episode, she awakens and on examination has no loss of motor or sensory function. Physical examination after the cur- rent episode shows that she is afebrile, with a pulse of 72/min, respirations of 17/min, and blood pressure of 120/80 mm Hg. Imaging studies reveal a 0.5-cm lesion in the head of the pancreas. The microscopic appearance of this lesion is shown in the figure. Which of the following pancreatic disorders is most likely to be present in this patient?
A Acute necrotizing pancreatitis
B Adenocarcinoma
C Cystic fibrosis
D Neuroendocrine tumor
E Pseudocyst
...
A 43-year-old man from Stockholm, Sweden, has had low-volume watery diarrhea for the past 3 months. He now has midepigastric pain. Over-the-counter antacid medications do not relieve the pain. On physical examination, he is afebrile; on palpation, there is no abdominal tenderness and no masses. An upper gastrointestinal endoscopy shows multiple 0.5- to 1.1-cm, shallow, sharply demarcated ulcerations in the first and second portions of the duodenum. He is given omeprazole. Three months later, repeat endoscopy shows that the ulcerations are still present. Which of the following analytes is most likely to be increased in his in serum or plasma?
A Gastrin
B Glucagon
C Insulin
D Somatostatin
E Vasoactive intestinal polypeptide (VIP)
...
A 39-year-old man has had headache, weakness, and a 5-kg weight gain over the past 3 months. He has experienced mental depression during the same period. On physical examination, his face is puffy. His temperature is 36.9° C and blood pressure is 160/75 mm Hg. He has cutaneous striae over the lower abdomen and ecchymoses scattered over the extremities. A radiograph of the spine shows a compressed fracture of T11. Laboratory findings show fasting plasma glucose level of 200 mg/dL, serum Na+ of 150 mmol/L, and serum K+ of 3.1 mmol/L. The plasma cortisol level is 38 μg/dL at 8:00 am and 37 μg/dL at 6:00 pm. Administration of low and high doses of dexamethasone fails to suppress the plasma cortisol level and excretion of urinary 17-hydroxycorticosteroids. The plasma corticotropin level is 0.8 pg/mL. Which of the following lesions is most likely to be present in this man?
A Adenohypophyseal adenoma
B Adrenal cortical adenoma
C Extra-adrenal pheochromocytoma
D Small cell carcinoma of the lung
E Thyroid medullary carcinoma
...
A 43-year-old woman has had absent menstrual cycles along with increasing weakness and weight gain over the past 5 months. She notes low back pain for the past week. On physical examination, vital signs include blood pressure of 155/95 mm Hg. She has a prominent fat pad in the posterior neck and back. Facial plethora, hirsutism, and abdominal cutaneous striae are present. Laboratory findings include Na+, 139 mmol/L; K+, 4.1 mmol/L; Cl-, 96 mmol/L; CO2, 23 mmol/L; glucose, 163 mg/dL; creatinine, 1.3 mg/dL; calcium, 8.9 mg/ dL; and phosphorus, 4.1 mg/dL. Her serum ACTH level is low. A radiograph of the spine shows decreased bone density with a compression fracture at T9. Which of the following radiographic findings is most likely to be present in this patient?
A Adrenal 10-cm solid mass with abdominal CT scan
B Decreased radionuclide uptake in a thyroid gland nodule
C Pulmonary 6-cm hilar mass on chest radiograph
D Retroperitoneal 5-cm mass at the aortic bifurcation on pelvic MRI scan
E Sella turcica enlargement with erosion on head CT scan
...
A 73-year-old woman has experienced malaise and a 10-kg weight loss over the past 4 months. She also has devel- oped a chronic cough during this time. She has a 100 pack-year history of smoking cigarettes. Physical examination shows muscle wasting and 4/5 motor strength in all extremities. Abdominal CT scan shows bilaterally enlarged adrenal glands. A chest radiograph shows a 6-cm perihilar mass on the right and prominent hilar lymphadenopathy. Laboratory studies show Na+, 118 mmol/L; K+, 6 mmol/L; Cl-, 95 mmol/L; CO2, 21 mmol/L; and glucose, 49 mg/dL. Her 8:00 am serum cortisol level is 9 ng/mL. What is the most likely diagnosis?
A Amyloidosis
B Ectopic corticotropin syndrome
C Meningococcemia
D Metastatic carcinoma
E Pituitary adenoma
...
A 28-year-old, otherwise healthy man has had headaches for the past 2 weeks. Physical examination yields no remarkable findings except for a blood pressure of 174/116 mm Hg. An abdominal CT scan shows an enlarged right adrenal gland. A right adrenalectomy is done; the figure shows the gross appearance of the specimen. Which of the following laboratory findings in his blood was most likely reported in this patient before surgery?
A Hyperglycemia
B Hyperkalemia
C Hyponatremia
D Low corticotropin level
E Low insulin level
F Low renin level
...
A 40-year-old woman has experienced increasingly frequent episodes of weakness accompanied by numbness and tingling in her hands and feet for the past year. On examination her blood pressure is 168/112 mm Hg. Laboratory studies show sodium, 142 mmol/L; potassium, 2.9 mmol/L; chloride, 104 mmol/L; HCO3-, 28 mmol/L; and glucose, 74 mg/dL. Her plasma renin activity is low. Which of the following radiologic findings is most likely to be present in this woman?
A Adrenal nodular enlargement
B Pancreatic mass
C Retroperitoneal mass
D Thyroid nodular enlargement
E Mediastinal mass
...
A 5-year-boy has developed features that suggest puberty over the past 6 months. On physical examination, the boy has secondary sex characteristics, including pubic hair and enlargement of the penis. Which of the following morphologic features is most likely to be seen in his adrenal glands?
A Cortical atrophy
B Cortical hyperplasia
C Cortical nodule
D Medullary atrophy
E Medullary hyperplasia
F Medullary nodule
...
A female infant is born at term to a 41-year-old Yupik woman after an uncomplicated pregnancy. Soon after birth, the neonate develops hypotension. Physical examination shows ambiguous genitalia with a prominent clitoris. Laboratory studies show Na+, 131 mmol/L; K+, 5.1 mmol/L; Cl-, 93 mmol/L; CO2, 18 mmol/L; glucose, 65 mg/dL; creatinine, 0.4 mg/dL; testosterone, 50 mg/dL (normal <30 mg/dL); and cortisol, 2 μg/dL. An abdominal ultrasound scan shows bilaterally enlarged adrenal glands. Which of the following enzyme deficiencies is most likely to be present in this infant?
A Aromatase
B 11-Hydroxylase
C 21-Hydroxylase
D 17α-Hydroxylase
E Oxidase
...
A 19-year-old, previously healthy woman collapsed after complaining of a mild sore throat the previous day. On examination she is hypotensive and febrile with purpuric skin lesions. Her peripheral blood smear shows schistocytes. Imaging studies show her adrenal glands are enlarged, and there are extensive bilateral cortical hemorrhages. Infection with which of the following organisms best accounts for these findings?
A Cytomegalovirus
B Histoplasma capsulatum
C Mycobacterium tuberculosis
D Neisseria meningitidis
E Streptococcus pneumoniae
...
A 29-year-old woman with systemic lupus erythematosus has been treated with corticosteroid therapy for several years because of recurrent lupus nephritis. She undergoes an emergency appendectomy for acute appendicitis. On postoperative day 2, she becomes somnolent and develops severe nausea and vomiting. She then becomes hypotensive. Blood cultures are negative, and laboratory studies now show Na+ of 128 mmol/L, K+ of 4.9 mmol/L, Cl- of 89 mmol/L, CO2 of 19 mmol/L, glucose of 52 mg/dL, and creatinine of 1.3 mg/dL. Which of the following morphologic findings in the adrenal gland cortex is most likely to be present in this patient?
A Adenoma
B Atrophy
C Carcinoma
D Caseating granulomas
E Hemorrhagic necrosis
F Nodular hyperplasia
...
A 55-year-old man has experienced increasing lethargy for the past 7 months. Physical examination shows hyperpigmentation of the skin. Vital signs include temperature of 36.9° C, pulse of 70/min, respirations of 14/min, and blood pressure of 95/65 mm Hg. Laboratory studies include a serum cortisol level of 3 μg/mL at 8:00 am with a serum corticotropin level of 65 pg/mL. Which of the following diseases most often occurs in patients with this disorder?
A Type 2 diabetes mellitus
B Classic polyarteritis nodosa
C Hashimoto thyroiditis
D Systemic lupus erythematosus
E Ulcerative colitis
...
A 44-year-old woman has become increasingly listless and weak and has had chronic diarrhea and a 5-kg weight loss over the past 7 months. She also notices that her skin seems darker, although she rarely goes outside because she is too tired for outdoor activities. On physical examination, she is afebrile, and her blood pressure is 85/50 mm Hg. A chest radiograph shows no abnormal findings. Laboratory findings include serum Na+, 120 mmol/L; K+, 5.1 mmol/L; glucose, 58 mg/dL; urea nitrogen, 18 mg/dL; and creatinine, 0.8 mg/ dL. The serum corticotropin level is 82 pg/mL. Which of the following is most likely to account for these findings?
A Adenohypophyseal adenoma
B Autoimmune destruction of the adrenals
C Pancreatic neuroendocrine tumor
D Metastatic carcinoma with lung primary
E Neisseria meningitidis infection of the adrenals
F Sarcoidosis of the lung and adrenals
...
A 37-year-old woman states that, although most of the time she feels fine, she has had episodes of palpitations, tachycardia, tremor, diaphoresis, and headache over the past 3 months. When her symptoms are worse, her blood pressure is measured in the range of 155/90 mm Hg. She collapses suddenly one day and is brought to the hospital, where her ventricular fibrillation is converted successfully to sinus rhythm. On physical examination, there are no remarkable findings. Which of the following laboratory findings is most likely to be reported in this patient?
A Decreased serum cortisol level
B Decreased serum glucose level
C Decreased serum potassium level
D Increased serum free T4 level
E Increased urinary free catecholamines
F Increased urinary homovanillic acid (HVA) level
...
A 25-year-old woman gives birth to a term infant following an uncomplicated pregnancy. On physical examination, the newborn is found to have an enlarged abdomen, but there are no other abnormal findings except for slightly elevated blood pressure. An abdominal ultrasound scan shows a right retroperitoneal mass in the adrenal gland. An increase in which of the following substances is most likely to be associated with the lesion in this neonate?
A Serum corticotropin (ACTH) level
B Serum cortisol level
C Serum growth hormone level
D Serum prolactin level
E Urinary free catecholamine level
F Urinary homovanillic acid (HVA) level
...
A 27-year-old man has headaches that have occurred frequently for the past 3 months. On physical examination, he is afebrile, and his blood pressure is 140/85 mm Hg. There are no neurologic abnormalities and no visual defects; however, he has an enlarged thyroid. Laboratory studies show that his serum calcitonin level is elevated. A total thyroidectomy is performed, and on sectioning, the thyroid has multiple tumor nodules in both lobes. Microscopically, the thyroid nodules are composed of nests of neoplastic cells separated by amyloid- rich stroma. The endocrinologist says that the patient's family members could be at risk for development of similar tumors and advises that they undergo genetic screening. Which of the following morphologic findings in the adrenal glands is most likely to be present in this patient?
A Bilateral 4-cm medullary masses
B Bilateral cortical atrophy
C Bilateral cortical nodular hyperplasia
D Solitary caseating granuloma
E Solitary 1-cm cortical mass with contralateral cortical atrophy
F Solitary 12-cm hemorrhagic cortical mass
...
A 26-year-old man developed sudden severe abdominal pain. On physical examination, he had marked abdominal tenderness and guarding. Laboratory studies showed serum glucose, 76 mg/dL; calcium, 12.2 mg/dL; phosphorus, 2.6 mg/dL; creatinine, 1.1 mg/dL; and parathyroid hormone, 62 pg/mL (normal range 9 to 60 pg/mL). During surgery, four enlarged parathyroid glands were found and excised, with re-implantation of one half of one gland. After the surgery, his serum calcium concentration returned to normal. Three years later, he had an episode of upper gastrointestinal hemorrhage. An endoscopy and biopsy specimen showed multiple benign gastric ulcerations. Abdominal MRI indicated multiple 1- to 2-cm mass lesions in the pancreas. He underwent surgery, and multiple tumors were found. Which of the following additional neoplasm lesions is he most likely to have?
A Adrenal pheochromocytoma
B Endometrial carcinoma
C Pituitary adenoma
D Pulmonary small cell anaplastic carcinoma
E Thyroid medullary carcinoma
...
A 10-year-old boy has been bothered by frequent headaches for the past 5 months. Physical examination yields no specific findings. Laboratory studies show normal electrolyte levels. CT scan of the head shows no bony abnormalities and no intracranial hemorrhage. MRI of the brain shows a 2-cm solid mass without calcifications or cystic change in the area inferior to the splenium of the corpus callosum, superior to the collicular plate, and between the right and left thalamic pulvinar regions. Because of the location, the mass is difficult to remove completely. Which of the following neoplasms is most likely to be present in this child?
A Craniopharyngioma
B Hypothalamic glioma
C Lymphoblastic lymphoma
D Metastatic carcinoma
E Pineoblastoma
F Prolactinoma
...
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