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Pathology Pre-test: Endocrine System

Terms in this set (29)

A 59-year-old woman presents with headaches and decreasing vision over the past several months. Her children state that she has been bumping into things recently and does not seem to see them when they are not directly in front of her. Physical examination is unremarkable except for the visual field abnormality illustrated in the picture. Her visual problems are most likely to be caused by a tumor originating in which one of the following anatomic areas?
a. Parietal lobe
b. Pineal gland
c. Pituitary gland
d. Posterior orbit
e. Temporal lobe
c. Pituitary gland
The visual pathway extends from the retina through the optic nerve, then the optic chiasm, through the optic tract, through the lateral geniculate body, and then through the optic radiations of the temporal and parietal lobes to end in the occipital lobes. Lesions in any of these areas produce characteristic visual field defects. For example, bitemporal hemianopsia (loss of vision in the periphery, also called "tunnel vision") is classically produced by lesions that involve the optic chiasm. The pituitary gland, which normally weighs about 0.5 g, lies in a bone depression (the sella turcica) and is covered by dura (diaphragma sellae). Anterior to the diaphragma sellae is the optic chiasm. Pituitary tumors may easily compress the optic chiasm and result in bilateral loss of peripheral vision.
Involvement of the optic nerve produces blindness in one eye (mononuclear anopsia), while involvement of the optic tract on one side results in homonymous hemianopsia (loss of the same side of the visual field in both eyes). A lesion involving the temporal lobe optic radiations produces a homonymous superior field defect, while a lesion involving the parietal lobe optic radiations produces a homonymous inferior field defect.
A 25-year-old woman who has never been pregnant presents with amenorrhea for 3 months and a milky discharge from her nipple. She states that her menstrual cycles have been irregular for the past year. Laboratory tests show that her serum LH and estradiol levels are below normal, and a pregnancy test is negative. Which of the following is the most likely cause of these signs and symptoms?
a. Craniopharyngioma of the hypothalamus
b. Germinoma of the pineal gland
c. Islet cell adenoma of the pancreas
d. Medullary carcinoma of the thyroid gland
e. Prolactinoma of the pituitary gland
e. Prolactinoma of the pituitary gland
Pituitary adenomas are the most common neoplasms of the pituitary gland. These benign neoplasms are classified according to the hormone or hormones that are produced by the neoplastic cells. The cell types, in order of decreasing frequency, are the following: lactotrope adenomas (which secrete prolactin), null cell adenomas (which do not secrete hormones), somatotrope adenomas (which secrete growth hormone), corticotrophic adenomas (which secrete ACTH), gonadotrope adenomas (which secrete FSH and LH), and thyrotrope cell adenomas (which secrete TSH). Prolactin- secreting tumors (lactotrope adenomas or prolactinomas) produce symptoms of hypogonadism and galactorrhea (milk secretion not associated with pregnancy). In females this hypogonadism produces amenorrhea and infertility, while in males it produces impotence and decreased libido. The same symptoms that are seen with a prolactin-secreting pituitary adenoma can also be produced by certain drugs, such as methyldopa and reserpine.
A 42-year-old man presents with increasing fatigue and occasional headaches. He states that recently he has had to change his shoe size from 9 to 10, and he also thinks that his hands and jaw are now slightly larger. Physical examination reveals a prominent forehead and lower jaw, enlarged tongue, and large hands and feet. Initial laboratory examination reveals increased serum glucose. Which of the following is the most likely explanation for this constellation of clinical findings?
a. Acromegaly
b. Apoplexy
c. Cretinism
d. Diabetes
e. Gigantism
a. Acromegaly
The second most common type of functioning pituitary adenoma is a growth-hormone--secreting somatotropic adenoma. This tumor can produce gigantism if it occurs in children prior to the closure of the epiphyseal plates or acromegaly if it occurs in adults after the closure of the epiphyseal plates. The latter is characterized by cartilaginous-periosteal soft tissue growth of the distal extremities (acromegaly) and growth of the skull and face bones. Additional findings in patients with excess growth hormone production include thickening of the skin, diabetes mellitus, and enlargement of the viscera, including increased size of the heart, kidneys, liver, and spleen. Cardiac failure is usually the mechanism of death. In contrast, cretinism is caused by a deficiency of thyroid hormone in infants, while apoplexy refers to the sudden loss of sensation and consciousness, usually caused by pressure on the brain, or referring to infarction of the pituitary.
A 25-year-old woman presents with the acute onset of cessation of lactation. She delivered her first child several months ago and has been breast-feeding since then. She reports that she has not menstruated since the delivery. She also says that lately she has been tired and has been "feeling cold" all of the time. Laboratory workup reveals a deficiency of ACTH and other anterior pituitary hormones. Which of the following is the most likely cause of this patient's signs and symptoms?
a. Craniopharyngioma
b. Cushing's disease
c. Empty sella syndrome
d. Nonsecretory chromophobe adenoma
e. Sheehan's syndrome
e. Sheehan's syndrome
Hypopituitarism results from destructive processes that involve the adeno-hypophysis (anterior pituitary). These processes may be acute (sudden) or chronic. Sheehan's syndrome, also known as postpartum pituitary necrosis, results from the sudden infarction of the anterior lobe of the pituitary. This can occur with obstetric complications, such as hemorrhage or shock. The pituitary gland normally doubles in size during pregnancy; hypovolemia during delivery decreases blood flow and may result in infarction of the anterior pituitary. Sheehan's syndrome produces symptoms of hypopituitarism. The initial sign is cessation of lactation, which may be followed by secondary amenorrhea due to the loss of gonadotropins. Other signs of hypopituitarism include hypothyroidism and decreased functioning of the adrenal gland. Acute destruction of the pituitary is also associated with DIC and thrombosis of the cavernous sinus. Chronic causes of hypopituitarism include nonsecretory chromophobe pituitary adenomas, empty sella syn- drome, and suprasellar (hypothalamic) tumors. Nonsecretory chromophobe adenomas present as space-occupying lesions that cause decreased hormone production. The gonadotropins are lost first, which results in signs of hypogonadism. Types of chromophobe adenomas include null cell adenomas (no cytoplasmic granules), chromophobes (sparse granules), and oncocytic adenomas (increased cytoplasmic mitochondria). The term pituitary apoplexy refers to spontaneous hemorrhage into a pituitary tumor, while the empty sella syndrome is caused by a defective diaphragma sellae, which permits CSF from the third ventricle to enter the sella. It may also be secondary to infarction or necrosis. A CT scan reveals the sella to be enlarged or to appear empty.
A 49-year-old man who smokes two packs of cigarettes a day presents with a lung mass on x-ray and recent weight gain. Laboratory examination shows hyponatremia with hyperosmolar urine. Which of the following is the most likely cause of these clinical findings?
a. Renal failure
b. Pituitary failure
c. Conn's syndrome
d. Cardiac failure
e. Excess ADH
e. Excess ADH
The syndrome of inappropriate antidiuretic hormone (SIADH) is an important cause of dilutional hyponatremia that has been identified in tumors of the thymus gland, malignant lymphoma, and pancreatic neoplasms. It occurs predominantly, however, as a result of ectopic secretion of ADH by small cell carcinomas of the lung. Since the tumor cells per se are autonomously producing ADH, there is no feedback inhibition from the hypothalamic osmoreceptors, and the persistent ADH effect on the renal tubules causes water retention even with concentrated urine, hence the term inappropriate ADH. Laboratory findings include low plasma sodium levels (dilutional hyponatremia), low plasma osmolality, and high urine osmolality caused by disproportionate solute excretion without water.
A 5-year-old girl is brought to the doctor's office by her mother, who states that the girl has been drinking a lot of water lately and has been urinating much more often than normal. Physical examination reveals a young girl whose eyes protrude slightly. An x-ray of her head reveals the presence of multiple lytic bone lesions involving her calvarium and the base of her skull, a biopsy of which reveals aggregates of Langerhans cells with intracytoplasmic Birbeck's granules. Which of the following sets of laboratory values is most consistent with the expected findings for this girl's disorder?
Serum Sodium--Urine
a. Hypernatremia--Low osmolarity and low specific gravity
b. Hypernatremia--High osmolarity and high specific gravity
c. Hyponatremia--Low osmolarity and low specific gravity
d. Hyponatremia--High osmolarity and high specific gravity
e. Normal--Normal osmolarity and normal specific gravity
a. Hypernatremia--Low osmolarity and low specific gravity
Diabetes insipidus (DI) results from a deficiency of antidi- uretic hormone (ADH) and is characterized by polyuria and polydipsia, but not the polyphagia or hyperglycemia of diabetes mellitus. The hallmark of DI is a dilute urine (low urine osmolarity) with an increased serum sodium (hypernatremia). Many cases of diabetes insipidus are of unknown cause (idiopathic), but DI may be the result of hypothalamic tumors, inflammations, surgery, or radiation therapy. Multifocal Langerhans cell histiocytosis (Hand-Schüller-Christian disease) is one of the Langerhans cell histiocytoses (histiocytosis X). The disorder, which usually begins between the second and sixth years of life, is associated with the characteristic triad of bone lesions (particularly in the calvarium and the base of the skull), diabetes insipidus, and exophthalmos.
A 28-year-old woman at 24 weeks of gestation of her first pregnancy has the following laboratory data: increased serum total thyroxine; normal free thyroxine; decreased resin triiodothyronine uptake; normal free thyroxine index; and normal thyroid-stimulating hormone. Which of the following is the best clinical interpretation of these laboratory findings?
a. Euthyroid individual with increased thyroid-binding globulin
b. Euthyroid individual with decreased thyroid-binding globulin
c. Hyperthyroid individual with decreased thyroid-binding globulin
d. Hypothyroid individual with decreased thyroid-binding globulin
e. Hypothyroid individual with increased thyroid-binding globulin
a. Euthyroid individual with increased thyroid-binding globulin
Tests used to determine thyroid function include serum thyroxine (T4), resin T3 uptake (RTU), thyroxine uptake (TU), free thyroxine index (FTI), and thyroid-stimulating hormone (TSH) levels. Serum T4 measures the total T4, which includes T4 bound to thyroid-binding globulin (TBG) and free T4. Therefore, increased total serum T4 levels can be from increased free T4 (such as Graves' disease) or from increased TBG. The resin T3 uptake (RTU) essentially measures the TBG concentration by measuring the binding of radioactive T3 to TBG; note that this is not the serum T3 concentration. The same thing is essentially determined using the thyroxine uptake (TU). These values then can be used to artificially determine the free thyroxine index (FTI), which is an estimate of the free thyroxine. The FTI (T7) can be determined using either T4 times TU or T4 times T3U.
To illustrate, consider the following. If a person is euthyroid, then their free T4 will be within normal limits. If the TBG in this person is normal, then the serum T4 will also be normal, but if their TBG is increased, which can be the result of increased estrogen from birth control pills or pregnancy, then the total serum T4 will be increased. Because the TBG is increased, however, the resin triiodothyronine uptake will be decreased. Because they are euthyroid and their free T4 is normal, then their TSH will also be normal. Note that the measurement of serum TSH levels is the best test to determine if thyroid function is normal or abnormal. A normal TSH level indicates that free T3 and free T4 levels in the serum are normal. Increased serum TSH indicates low free T3 and T4 levels (primary hypothyroidism), while decreased serum TSH levels indicate either decreased production by the pituitary (hypopituitarism) or increased thyroid production by the thyroid gland (hyperthyroidism).
An 8-month-old infant is being evaluated for growth and mental retardation. Physical examination reveals a small infant with dry, rough skin; a protuberant abdomen; periorbital edema; a flattened, broad nose; and a large, protuberant tongue. Which of the following disorders is the most likely cause of this infant's signs and symptoms?
a. Graves' disease
b. Cretinism
c. Toxic multinodular goiter
d. Toxic adenoma
e. Struma ovarii
b. Cretinism
The consequences of excess or inadequate thyroid hormone are directly attributed to abnormalities involving the normal functioning of thyroid hormones, such as regulation of body processes. For example, excess thy- roid hormone (hyperthyroidism) results in weight loss (increased lipolysis) despite increased food intake, heat intolerance, increased heart rate, tremor, nervousness, and weakness (due to loss in muscle mass). Inade- quate levels of thyroid hormone (hypothyroidism) produce different signs and symptoms in children than in older children and adults. In young chil- dren hypothyroidism produces cretinism, a disease that is characterized by marked retardation of physical and mental growth (severe mental retarda- tion). Patients develop dry, rough skin and a protuberant abdomen. Char- acteristic facial features include periorbital edema; a flattened, broad nose; and a large, protuberant tongue. In contrast, hypothyroidism in older chil- dren and adults produces myxedema. This disease is characterized by a decrease in the metabolic rate, which can result in multiple signs and symptoms, such as cold intolerance and weight gain. Neurologic features of this abnormality include slowing of intellectual and motor function (fatigue, lethargy, and slow speech), apathy, sleepiness, depression, para- noia, and prolonged relaxation phase in deep tendon reflexes ("hung-up" reflexes). Other signs and symptoms of hypothyroidism include dry skin and brittle hair, which can produce hair loss; decreased erythropoiesis, which produces a normochromic normocytic anemia; increased choles- terol, which increases the risk of atherosclerosis; and myxedema, which is the increased interstitial deposition of mucopolysaccharides. The latter abnormality can result in diffuse nonpitting edema of the skin, hoarseness, and enlargement of the heart. Other systems affected by hypothyroidism include the heart, the GI tract, and the GU tract. Patients may develop a slowed heart rate and decreased stroke volume (resulting in cool, pale skin) and constipation, as well as impotence (in men) or menorrhagia and anovulatory cycles (in women).
A 35-year-old woman presents with progressive muscle weakness and cold intolerance. Physical examination finds enlargement of her thyroid gland, which is rubbery in consistency. No lymphadenopathy is found. Laboratory evaluation finds decreased serum levels of both triiodothyronine (T3) and thyroxine (T4), but serum levels of thyroid-stimulating hormone (TSH) are increased. No thyroid-stimulating immunoglobulins are identified in the serum, but thyroidal peroxidase autoantibodies are present. Which of the following histologic findings is most consistent with a diagnosis of Hashimoto's thyroiditis?
a. Diffuse fibrous deposition between atrophic follicles
b. Follicular cell hyperplasia with scalloping of colloid
c. Granulomatous inflammation with multinucleated giant cells
d. Lymphoid infiltrate with scattered Hurthle cells
e. Parafollicular hyperplasia with deposition of amyloid
d. Lymphoid infiltrate with scattered Hurthle cells
Hashimoto's thyroiditis, one of the autoimmune thyroid diseases, is associ- ated with the HLA-B8 haplotype and high titers of circulating autoantibod- ies, including antimicrosomal, antithyroglobulin, and anti-TSH receptor antibodies. This abnormality, which is not uncommon in the United States, is characterized histologically by an intense lymphoplasmacytic infiltrate, with the formation of lymphoid follicles and germinal centers. This pro- duces destruction and atrophy of the follicles and transforms the thyroid follicular cells into acidophilic cells. There are many different names for these cells, including oxyphilic cells, oncocytes, and Hürthle cells. Not uncommonly, patients develop hypothyroidism as a result of follicle dis- ruption, and the manifestations consist of fatigue, myxedema, cold intoler- ance, hair coarsening, and constipation. Rarely, cases of Hashimoto's thyroiditis may develop hyperthyroidism (Hashitoxicosis), while the com- bination of Hashimoto's disease, pernicious anemia, and type I diabetes mellitus is called Schmidt's syndrome. This is one type of multiglandular syndrome.
Although subacute thyroiditis and Riedel's thyroiditis may have similar symptoms to Hashimoto's thyroiditis, biopsy findings in these disorders are distinctly different. Subacute (de Quervain's, granulomatous, or giant cell) thyroiditis is a self-limited viral infection of the thyroid. It typically follows an upper respiratory tract infection. Patients develop the acute onset of fever and painful thyroid enlargement and may develop a transient hypothyroidism. Histologically there is destruction of the follicles with a granulomatous reaction and multinucleated giant cells that surround frag- ments of colloid. One-half of patients with Riedel's thyroiditis are hypothy- roid, but, in contrast to the other types of thyroiditis, microscopic examination reveals dense fibrosis of the thyroid gland, often extending into extrathyroidal soft tissue. This fibrosis produces a rock-hard enlarged thyroid gland that may produce the feeling of suffocation. This combina- tion of signs and symptoms may be mistaken clinically for a malignant process. Additionally, these patients may develop similar fibrosis in the mediastinum or retroperitoneum. Subacute lymphocytic thyroiditis is also a self-limited, painless enlargement of the thyroid that is associated with hypothyroidism, but that lacks antithyroid antibodies or lymphoid germi- nal centers within the thyroid. Finally, follicular cell hyperplasia with scal- loping of colloid is characteristic of hyperthyroidism due to Graves' disease, while the extracellular deposition of amyloid in the thyroid gland is characteristic of medullary thyroid carcinoma.
A 29-year-old woman presents with nervousness, heat intolerance, and weight loss. Physical examination reveals the presence of exophthalmus, pretibial myxedema, and diffuse enlargement of the thyroid. Laboratory examination reveals elevated serum thyroxine (T4) and triiodothyronine (T3) levels, while the level of serum thyroid-stimulating hormone (TSH) is decreased. Histologic sections from her thyroid gland reveal increased cellularity with scalloping of the colloid at the margins of the follicles. Which of the following types of autoantibodies is most specific for this individual disease?
a. Antimicrosomal antibodies
b. Antithyroglobulin antibodies
c. Antithyroid peroxidase antibodies
d. TSH-receptor-blocking antibodies
e. TSH-receptor-stimulating antibodies
e. TSH-receptor-stimulating antibodies
Graves' disease, or diffuse toxic goiter, is one of the three most common disorders associated with thyrotoxicosis or hyperthyroidism (the other two are toxic multinodular goiter and toxic adenoma). This hyperfunctioning and hyperplastic diffuse goiter is accompanied by a characteristic triad of clinical findings: signs of hyperthyroidism, exophthalmus, and pretibial myxedema. Graves' disease is an autoimmune form of goiter caused by thyroid-stimulating immunoglobulins or thyroid-stimulating hormone (TSH) receptor antibodies. Autoantibodies to TSH receptor antigens are pro- duced because of a defect in antigen-specific suppressor T cells. The anti- bodies bind to TSH receptors on thyroid follicular cells and function as TSH, with resultant thyroid growth and hyperfunction. Such antibodies can be identified in almost all cases of Graves' disease. In contrast to these stimulating autoantibodies, Hashimoto's thyroiditis, an autoimmune cause of hypothyroidism, is associated with high titers of circulating blocking autoantibodies, such as antithyroglobulin, anti-TSH receptor, and antimi- crosomal antibodies.
A 58-year-old woman presents with increased "fullness" in her neck. Physical examination finds a single, nonfunctioning mass within the thyroid. Clinically she is found to be euthyroid and her serum TSH level is within normal limits. Histologic sections from this mass reveal a single nodule composed of follicles similar to normal thyroid tissue. The nodule is surrounded by a complete fibrous capsule that compresses adjacent normal thyroid tissue. Focal invasion into the capsule is found. Further evaluation of the tumor cells finds the presence of the PAX8-PPAR-gamma fusion gene. Which of the following is the most likely diagnosis?
a. Colloid carcinoma
b. Colloid goiter
c. Diffuse nontoxic goiter
d. Follicular adenoma
e. Follicular carcinoma
e. Follicular carcinoma
Follicular carcinoma is the second most common malignancy of the thyroid gland. These tumors present as slowly enlarging painless nodules that usually are found to be "cold" (nonfunctioning) nodules with thyroid scans. The histology of follicular carcinoma is similar to follicular adenoma and this type of malignancy may have a well-defined capsule. Invasion into blood vessels or the capsule must be present to diagnosis follicular carcinoma. There are two basic pathways that lead to the development of follicular carcinomas of the thyroid. One involves mutations of the RAS family of oncogenes, while the other involves a unique translocation between PAX8 and the peroxisome proliferator-activated receptor gamma (PPAR gamma), which forms a PAX8-PPAR-gamma fusion gene.
The PAX (paired box) genes are a family of related genes that code for transcription factors important for tissue development. Abnormalities of these PAX genes are associated with various diseases: PAX-2 with the "renal- coloboma" syndrome; PAX-3 with the Waardenburg syndrome (white forelocks of hair; eye colors don't match); PAX-5 with lymphoplasmacytoid lymphoma; PAX-6 with aniridia and Wilm's tumor; PAX-8 with follicular thyroid carcinoma; and PAX-9 with congenital absence of teeth.
Note that the clinical term goiter is used to describe any enlargement of the thyroid. Most patients with goiter are euthyroid (nonfunctional goiter), as hyperthyroidism (toxic goiter) is relatively rare. In the early stages of goiter formation, there is diffuse hyperplasia of the small thyroid follicles, which histologically resembles the changes of Graves' disease. This early stage is called a diffuse nontoxic goiter or simple goiter. The thyroid gland then undergoes repeated episodes of involution and hyperplasia. Over time this produces an enlarged multinodular goiter that histologically consists of multiple nodules, some of which consist of colloid-filled enlarged follicles and others of which show hyperplasia of small follicles lined by active epithelium. There are also areas of fibrosis, hemorrhage, calcification, and cystic degeneration. The last stage of goiter formation consists of nodules composed primarily of enlarged colloid-filled follicles. This stage is called a colloid goiter. Finally, note that colloid carcinoma is a type of malignancy of the breast, not the thyroid gland.
A 45-year-old woman presents for a routine physical examination and is found to have several small masses within the right lobe of her thyroid gland. No enlarged lymph nodes are found. Her thyroid gland is resected surgically and histologic sections from the tumor masses reveal multiple papillary structures and scattered small, round, laminated calcifications. Which of the following histologic changes is most likely to be present within these tumor masses?
a. Amyloid stromal invasion by malignant C cells
b. Blood vessel and capsular invasion by malignant follicles
c. Optically clear nuclei with longitudinal nuclear grooves
d. Sheets of small round cells with cytoplasmic glycogen
e. Undifferentiated anaplastic cells with giant cell formation
c. Optically clear nuclei with longitudinal nuclear grooves
The four major histologic subtypes of thyroid carcinoma are papillary carcinoma, follicular carcinoma, medullary carcinoma, and undifferentiated (anaplastic) carcinoma. Papillary carcinomas of the thyroid are composed of papillary structures with fibrovascular cores, while follicular carcinomas typically show a microfollicular pattern. It is important prognostically to differentiate papillary carcinomas from follicular carcinomas, as papillary carcinomas tend to be indolent (up to 80% survival at 10 years), while follicular carcinomas are much more aggressive (5-year mortality of up to 70%). Follicular areas may be present within a papillary carcinoma and in fact may be quite extensive. If present, these changes can make diagnosis difficult. It is important to recognize this follicular variant of papillary carcinoma because its behavior remains similar to that of indolent papillary carcinoma. Features consistent with papillary carcinoma, even in predominantly follicular areas, include optically clear nuclei ("ground glass," "Orphan Annie eyes"), nuclear grooves, calcospherites (psammoma bodies), and intranuclear cytoplasmic pseudoinclusions.
In contrast to the histologic features of papillary carcinoma, follicular carcinoma of the thyroid has a histology that is similar to a follicular adenoma, but capsular and blood vessel invasion is present. Medullary carcinoma is characterized by its amyloid stroma, its genetic (familial) associations, and its elaboration of calcitonin and other substances. It is a malignancy that originates from the parafollicular C cells. Undifferentiated (anaplastic) carcinoma, seen in individuals over the age of 50, is characterized by anaplastic spindle or giant cells with frequent mitoses. This tumor is characterized by rapid growth and a poor prognosis.
A 37-year-old man presents with a single, firm mass within the thy- roid gland. This patient's father developed a tumor of the thyroid gland when he was 32 years of age. Histologic examination of the mass in this 37- year-old man reveals organoid nests of tumor cells separated by broad bands of stroma, as seen in the photomicrograph. The stroma stains positively with Congo red stain and demonstrates yellow-green birefringence. Which of the following is the most likely diagnosis?
a. Follicular carcinoma
b. Papillary carcinoma
c. Squamous cell carcinoma
d. Medullary carcinoma
e. Anaplastic carcinoma
d. Medullary carcinoma
The development of a thyroid mass in a young person who gives a familial history for a similar lesion should raise high clinical suspicion of the possibility that the mass is a medullary carcinoma of the thyroid (MCT). MCT is a tumor of the parafollicular (C) cells of the thyroid and as such is associated with secretion of calcitonin. The procalcitonin is deposited in the stroma of the tumor and appears as amyloid, which stains positively with Congo red stain. The tumor cells have peripheral nuclei that give them a plasmacytoid appearance when viewed cytologically with fine-needle aspiration (FNA). Electron microscopy reveals membrane-bound dense-core neurosecretory granules in the neoplastic cells. MCT may secrete other substances in addi- tion to calcitonin, such as ACTH, CEA, and serotonin. It is also associated with paraneoplastic syndromes, such as carcinoid syndrome (due to serotonin) and Cushing's syndrome (due to ACTH).
A 21-year-old woman presents with the acute onset of perioral tingling and muscle cramps involving both of her hands. Physical examination finds an anxious woman with an increased respiratory rate, while laboratory examination reveals decreased arterial PCO2, decreased bicarbonate, and an increased blood pH. The respiratory alkalosis in this individual caused tetany by decreasing the ionized serum levels of what substance?
a. Calcium
b. Chloride
c. Magnesium
d. Potassium
e. Sodium
a. Calcium
Hypocalcemia results from either parathyroid causes (primary hypoparathyroidism) or non-parathyroid causes, which include hypoalbuminemia, hypomagnesemia, decreased vitamin D, chronic renal failure, and hyperventilation. Hypocalcemia may produce numbness and tingling of the hands, feet, and lips or tetany (spontaneous tonic muscular contractions). Two clinical tests to demonstrate tetany are Chvostek's sign (tapping on the facial nerve pro- duces twitching of the ipsilateral facial muscles) and Trousseau's sign (inflating a blood pressure cuff for several minutes produces painful carpal muscle contractions). Hypocalcemia produces tetany by the following pathomechanism. A low ionized calcium allows sodium ions to preferentially enter channels in the cell membranes of neurons. This depolarizes the nerve and causes tetanic spasms of muscle. Patients who hyperventilate develop respiratory alkalosis because they are blowing off CO2. This increased pH increases the negative charge on albumin, which increases the amount of calcium bound to albumin. Although the total serum calcium levels are not changed, the ionized calcium is decreased and this produces tetany.
A 52-year-old woman presents with nausea, fatigue, muscle weakness, and intermittent pain in her left flank. Laboratory examination reveals an increased serum calcium and a decreased serum phosphorus. The patient's plasma parathyroid hormone levels are increased, but para-thyroid hormone-related peptide levels are within normal limits. Urinary calcium is increased, and microhematuria is present. Which of the following is the most likely cause of this patient's signs and symptoms?
a. Primary hyperparathyroidism
b. Primary hypoparathyroidism
c. Pseudohypoparathyroidism
d. Secondary hyperparathyroidism
e. Secondary hypoparathyroidism
a. Primary hyperparathyroidism
Hyperparathyroidism is caused by excess production of parathyroid hormone (PTH). In patients with hyperparathyroidism, it is important to distinguish primary hyperparathyroidism from secondary hyperparathyroidism. Both forms may be associated with the development of bone lesions, but excess PTH production in primary hyperparathyroidism leads to different laboratory values than those seen with secondary hyperparathyroidism. Increased levels of PTH in primary hyperparathyroidism result in increased serum calcium (hypercalcemia) and decreased serum phosphorus. The serum calcium levels are elevated because of increased bone resorption and increased intestinal calcium absorption, the result of increased activity of vitamin D. PTH also increases calcium reabsorption in the distal renal tubule, but, because the filtered load of calcium exceeds the ability for reabsorption, calcium is increased in the urine (hypercalciuria). PTH also increases urinary excretion of phosphate. The excess calcium in the urine predisposes to renal stone formation, especially calcium oxalate or calcium phosphate stones. Urinary stones can produce flank pain and hematuria. This is the most common presentation for patients with hyperparathyroidism. The hypercalcemia of hyperparathyroidism may also cause peptic ulcer disease due to the stimulation of gastrin release and increased acid secretion from the parietal cells. The hypercalcemia also results in muscle weakness, fatigue, and hypomotility of the GI tract, which can lead to constipation and nausea. Alterations of mental status are also common.
In contrast to primary hyperparathyroidism, secondary hyper-parathyroidism results from hypocalcemia. This causes secondary hyper- secretion of PTH and produces the combination of hypocalcemia and increased PTH production. It is primarily found in patients with chronic renal failure. Patients with hypoparathyroidism develop hypocalcemia and hyperphosphatemia but have normal serum creatinine levels. Primary hypo- parathyroidism and pseudohypoparathyroidism also result in decreased 24-h excretion of calcium and phosphate.
A 65-year-old man presents with bone pain and is found to have hypocalcemia and increased parathyroid hormone. Surgical exploration of his neck finds all four of his parathyroid glands to be enlarged. Which of the following disorders is the most likely cause of this patient's enlarged parathyroid glands?
a. Primary hyperplasia
b. Parathyroid adenoma
c. Chronic renal failure
d. Parathyroid carcinoma
e. Lung carcinoma
c. Chronic renal failure
Parathyroid hyperplasia may be associated with either primary or secondary hyperparathyroidism. In contrast to primary hyperparathyroidism, secondary hyperparathyroidism results from hypocalcemia and causes secondary hypersecretion of parathyroid hormone (PTH). This results in the combination of hypocalcemia and increased PTH. This abnormality is principally found in patients with chronic renal failure, where phosphate retention is thought to cause hypocalcemia. Since the failing kidney is not able to synthesize 1,25-dihydroxycholecalciferol, the most active form of vitamin D, this deficiency leads to poor absorption of calcium from the gut and relative hypocalcemia, which stimulates excess PTH secretion. Chronic renal failure is the most important cause, but secondary hyperparathyroidism also occurs in vitamin D deficiency, malabsorption syndromes, and pseudohypoparathyroidism. In any of the causes of parathyroid hyperplasia, all four parathyroid glands are typically enlarged. Parathyroid hyperplasia can be differentiated from parathyroid adenomas by the fact that parathyroid hyperplasia, either primary or secondary, results in enlargement of all four glands, while a parathyroid adenoma or parathyroid carcinoma produces enlargement of only one gland. In most cases the other three glands are smaller than normal.
A 65-year-old woman presents with numbness and tingling of her hands, feet, and lips. Physical examination reveals hyperactivity of her muscles, which is illustrated by a positive Chvostek's sign. Which one of the labeled boxes in the graph below best depicts the expected serum levels of calcium and parathyroid hormone in this individual?
a. Box A
b. Box B
c. Box C
d. Box D
e. Box E
c. Box C
To summarize the diseases of the parathyroid glands, since serum calcium levels are affected by serum PTH levels, plotting serum calcium levels and serum PTH on a graph will separate the different abnormalities of PTH functioning into different areas of the graph. Increased levels of PTH (hyperparathyroidism) may be either primary or secondary. Primary hyperparathyroidism is associated with increased PTH and increased calcium (area B), while secondary hyperparathyroidism is associated with increased PTH and decreased or normal calcium levels (boxes E and D, respectively). This can be seen in patients with a deficiency of 1-α-hydroxylase, because decreased active vitamin D levels produce decreased absorption of calcium, hypocalcemia, and resultant hyperparathyroidism.
Primary hypoparathyroidism refers to decreased levels of PTH and decreased levels of calcium (box C). Causes of primary hypoparathyroidism include iatrogenic factors, such as surgical accident during thyroidectomy, congenital abnormalities (DiGeorge's syndrome), and type I polyglandular autoimmune syndrome. Patients with the latter abnormality have at least two of the triad of Addison's disease, hypoparathyroidism, and mucocutaneous candidiasis. Pseudo-hypoparathyroidism refers to decreased levels of calcium and increased levels of PTH (box E, which is the same as hyperparathyroidism). Pseudo-hyperparathyroidism would theoretically refer to decreased levels of PTH and increased levels of calcium (box A). This combination does not occur with diseases of the parathyroid glands, but instead can be seen in patients with hypercalcemia as the result of production of a substance with parathyroid hormone like function (paraneoplastic syndrome). This substance is called parathyroid-hormone-related protein. In these patients, serum levels of PTH are decreased because of the high levels of calcium.
A 17-year-old woman with mental retardation presents with cramping in her legs and numbness and tingling around her mouth. Physical examination reveals a short, obese young woman who has several subcutaneous calcified masses. Laboratory examination reveals hypocalcemia despite her PTH being elevated. X-rays of her hands and feet reveal shortened fourth and fifth metacarpal and metatarsal bones. Which of the following is the basic defect causing this disorder?
a. Decreased production of ACTH by the anterior pituitary
b. Defective binding of hormones to guanine nucleotide-binding proteins
c. Malformation of pharyngeal pouches 3 and 4
d. Secretion of parathyroid-related peptide by a benign parathyroid adenoma
e. The presence of autoantibodies to the parathyroid hormone receptor
b. Defective binding of hormones to guanine nucleotide-binding proteins
Hypoparathyroidism may be caused by either decreased secretion of parathyroid hormone (PTH) or end organ insensitivity to PTH (pseudo-hypoparathyroidism), both of which are associated with hypocalcemia and hyperphosphatemia. Many patients with pseudo-hypoparathyroidism have a defect in binding of many hormones to guanine nucleotide-binding protein (G protein). These hormones include PTH, thyroid-stimulating hormone, glucagon, and the gonadotropins follicle-stimulating hormone and luteinizing hormone. These patients have characteristic signs and symptoms including short stature, round face, short neck, reduced intelligence, and abnormally short metacarpal and metatarsal bones. In contrast to patients with hypothyroidism caused by decreased levels of PTH, patients with pseudo-hypoparathyroidism (Albright's hereditary osteodystrophy) have normal or increased levels of circulating PTH and in fact have hyperparathyroidism.
An XX infant is found to have external male genitalia and internal female genitalia. Physical examination reveals decreased blood pressure, while laboratory examination reveals a serum sodium level of 132 meq/L. Additionally, bilateral adrenal cortical hyperplasia is present. A deficiency of which of the following enzymes is most likely to produce the clinical findings in this infant?
a. 3-β-dehydrogenase
b. 11-hydroxylase
c. 17-hydroxylase
d. 21-hydroxylase
e. 1-α-hydroxylase
d. 21-hydroxylase
In the adrenal cortex, cholesterol is converted into either mineralocorticoids (aldosterone) in the zona glomerulosa, glucocorticoids (cortisol) in the zona fasciculata, or sex steroid precursors in the zona reticularis. Congenital adrenal hyperplasia (CAH) is a syndrome that results from a defect in the synthesis of cortisol. This leads to excess ACTH secretion by the anterior pituitary and resultant adrenal hyperplasia. The defect in the synthesis of cortisol is the result of a deficiency in one of the enzymes in the normal pathway of cortisol synthesis, such as 21-hydroxylase or 11-hydroxylase. Most cases of CAH result from a deficiency of 21-hydroxylase. Two forms of this deficiency include salt-wasting adrenogenitalism and simple virilizing adrenogenitalism. The salt-wasting syndrome results from a complete lack of the hydroxylase. There is no synthesis of mineralocorticoids or glucocorticoids in the adrenal cortex. Decreased mineralocorticoids cause marked sodium loss in the urine, hyponatremia, hyperkalemia, acidosis, and hypotension.
Because of the enzyme block there is increased formation of 17- hydroxyprogesterone, which is then shunted into the production of testosterone. This may cause virilism (pseudohermaphroditism) in female infants. That is, XX females with CAH develop ovaries, female ductal structures, and external male genitalia. Much more often there is only a partial deficiency of 21-hydroxylase, which leads to decreased production of both aldosterone and cortisol. The decreased cortisol levels cause increased production of ACTH by the pituitary, which results in adrenal hyperplasia, enough to maintain adequate serum levels of aldosterone and cortisol. In contrast to a complete deficiency of 21-hydroxylase, there is no sodium loss with a partial deficiency of 21-hydroxylase. The excess stimulation by ACTH, however, leads to increased production of androgens, which may cause virilism in female infants.
A deficiency of 11-hydroxylase, which is rare, also leads to decreased cortisol production and increased ACTH secretion. This in turn leads to the accumulation of deoxycorticosterone (DOC) and 11-deoxycortisol, both of which are strong mineralocorticoids. This results in increased sodium retention by the kidneys and hypertension. Patients also develop hypokalemia and virilization due to androgen excess. Patients with a deficiency of 17- hydroxylase also exhibit impaired cortisol production, increased ACTH, and secondary increased DOC. These patients, however, cannot synthesize normal amounts of androgens and estrogens. This is because the gene that codes for 17-hydroxylase is the same for the enzyme in the adrenal cortex and the gonads, and the deficiency is the same in both organs. Because of decreased sex hormones, genotypic females develop primary amenorrhea and fail to develop secondary sex characteristics, while genotypic males present as pseudohermaphrodites. Additionally, the plasma LH levels are increased due to decreased feedback inhibition.
A 55-year-old woman presents with increasing muscle weakness and fatigue. Physical examination finds an obese adult woman with purple abdominal stria and increased facial hair. The excess adipose tissue is mainly distributed in her face, neck, and trunk. Laboratory evaluation finds increased plasma levels of cortisol and glucose. Which of the following is the most likely diagnosis?
a. Addison's disease
b. Bartter's syndrome
c. Conn's syndrome
d. Cushing's syndrome
e. Schmidt's syndrome
d. Cushing's syndrome
The clinical effects of excess cortisol are called Cushing's syndrome. Many of the symptoms of Cushing's syndrome that result from excess cortisol production can be directly related to the normal function of cortisol. Because cortisol is a glucocorticoid, its major function involves the maintenance of normal blood glucose levels. In this regard cortisol increases gluconeogenesis and glycogen storage in the liver. To provide the protein for liver gluconeogenesis, muscle is broken down. Because muscle is primarily located in the extremities, patients lose muscle in the extremities. This produces muscle wasting and proximal muscle weakness. Cortisol, in contrast to insulin, inhibits glucose uptake by many tissues. Therefore, excess cortisol causes symptoms of glucose intolerance, hyperglycemia, and diabetes mellitus. Cortisol also stimulates the appetite and lipogenesis in certain adipose tissues (the face and trunk), while promoting lipolysis in the extremities. Therefore, excess cortisol is associated with truncal obesity, "moon" face, and "buffalo hump." Excess cortisol inhibits fibroblasts, which in turn leads to loss of collagen and connective tissue. This produces thinning of the skin and weakness of blood vessels, which in turn results in easy bruising (ecchymoses), purple abdominal striae, and impaired wound healing. Cortisol also decreases the intestinal absorption of calcium, decreases the renal reabsorption of calcium and phosphorus, and increases the urinary excretion of calcium (hypercalcinuria). The combination of decreased bone formation and increased bone resorption with excess cortisol produces osteoporosis (decreased bone mass). Hypertension also occurs in a majority of patients with Cushing's syndrome; the exact mechanism is unknown. Cortisol enhances erythropoietin function, resulting in secondary polycythemia, which is seen clinically as plethora. Cortisol also normally functions to inhibit many inflammatory and immune reactions. Hypercortisolism produces decreased neutrophil adhesion in blood vessels and increased destruction of lymphocytes and eosinophils. This results in an absolute neutrophilia, absolute lymphopenia, eosinopenia, and increased vulnerability to microbial infections. Patients with Cushing's syndrome also develop psychiatric symptoms that include euphoria, mania, and psychosis. Gonadal dysfunction also is frequent, which in pre- menopausal women leads to hirsutism, acne, amenorrhea, and infertility.
In contrast to Cushing's syndrome, which results from excess cortisol, Conn's syndrome results from excess aldosterone. Addison's disease results from hypofunctioning, not hyperfunctioning, of the adrenal cortex. It most commonly results from autoimmune destruction of the adrenal cortex. Finally, Schmidt's syndrome, which is a type of polyglandular autoimmune syndrome, is characterized by the combination of Hashimoto's disease, pernicious anemia, and type I diabetes mellitus.
Which box in the schematic represents the most likely serum findings for an individual on long-term exogenous glucocorticoid administration?
a. Box A
b. Box B
c. Box C
d. Box D
e. Box E
e. Box E
Increased serum cortisol, which produces clinical symptoms of Cushing's syndrome, may be secondary to excess ACTH production or independent of ACTH production. Causes of increased cortisol levels that are independent of ACTH (box E in the diagram) may involve abnormalities of the adrenal gland itself, such as a cortical adenoma or cortical carcinoma, or they may involve exogenous (iatrogenic) corticosteroids. Increased cortisol levels that are dependent on ACTH are associated with excess ACTH production (box B in the diagram) and may result from an abnormality of the pituitary itself, such as a tumor of the anterior pituitary (Cushing's disease), or from the ectopic production of ACTH outside of the pituitary, such as paraneoplastic syndromes, one example being small cell carcinoma of the lung.
The high-dose dexamethasone suppression test is used to distinguish ACTH-induced Cushing's disease from the ACTH-independent type. Dexamethasone suppresses pituitary ACTH production, but has no effect on the adrenal gland. Therefore decreased cortisol levels with dexamethasone administration indicate the anterior pituitary as the cause of the ACTH- induced cortisol overproduction.
A 47-year-old man presents with headaches, muscle weakness, and leg cramps. He is not currently taking any medications. Physical examination finds a thin adult man with mild hypertension. Laboratory examination reveals slightly increased sodium, decreased serum potassium level, and decreased hydrogen ion concentration. Serum glucose levels are within normal limits. A CT scan reveals a large tumor involving the cortex of his left adrenal gland. Which of the following combinations of serum laboratory findings is most likely to be present in this individual?
a. Decreased aldosterone with increased renin
b. Decreased cortisol with decreased ACTH
c. Increased aldosterone with decreased renin
d. Increased cortisol with increased ACTH
e. Increased deoxycorticosterone with increased cortisol
c. Increased aldosterone with decreased renin
Excess aldosterone secretion may be due to an abnormality of the adrenal gland (primary aldosteronism) or an abnormality of excess renin secretion (secondary aldosteronism). Causes of primary hyperaldosteronism (Conn's syndrome), which is independent of the renin-angiotensin-aldosterone (RAA) system, include adrenal cortical adenomas (most commonly), hyper-plastic adrenal glands, and adrenal cortical carcinomas. These diseases are associated with decreased levels of renin. The signs of primary hyper-aldosteronism include weakness, hypertension, polydipsia, and polyuria. The underlying physiologic abnormalities include increased serum sodium and decreased serum potassium, the latter due to excessive potassium loss by the kidneys, which together with the loss of hydrogen ions produces a hypokalemic alkalosis. The elevated level of serum sodium causes expansion of the intravascular volume. In contrast to Conn's syndrome, secondary hyper-aldosteronism results from conditions causing increased levels of renin, such as renal ischemia, edematous states, and Bartter's syndrome. Causes of renal ischemia include renal artery stenosis and malignant nephrosclerosis, while Bartter's syndrome results from renal juxtaglomerular cell hyperplasia.
A 42-year-old man presents with weakness and dizziness associated with stress. Physical examination reveals a slightly decreased blood pressure along with a diffuse increase in skin pigmentation. Laboratory examination reveals hyponatremia and hyperkalemic acidosis with decreased aldosterone, decreased cortisol, decreased glucose, increased ACTH, decreased sex steroids, and increased LH and FSH. Thyroid function tests are found to be within normal limits. Which of the following is the most likely cause of this patient's signs and symptoms?
a. A benign adenoma of the adrenal cortex
b. A malignant tumor of the adrenal medulla
c. Autoimmune destruction of the adrenal cortex
d. Bilateral hyperplasia of the adrenal cortex
e. Tuberculosis of the adrenal medulla
c. Autoimmune destruction of the adrenal cortex
Hypo-functioning of the cortex of the adrenal gland (adrenocortical insufficiency) may be the result of abnormalities involving either the adrenal gland itself (primary adrenocortical insufficiency) or the pituitary gland, which controls the adrenal (secondary adrenocortical insufficiency). Primary insufficiency may arise from either an acute process or a chronic process. Causes of primary acute adrenocortical insufficiency include acute hemorrhagic necrosis of the adrenals, seen in children as Waterhouse-Friderichsen syndrome. This syndrome is most commonly due to Neisseria meningitidis septicemia, which is characterized by meningitis, septicemia, DIC, and hypovolemic shock. Acute adrenocortical insufficiency may also occur with too rapid a withdrawal of steroid therapy if a patient has additional stress. Causes of primary chronic adrenocortical insufficiency (Addison's disease) include autoimmune adrenalitis, infections, amyloidosis, and metastatic cancer. Previously the most common cause of Addison's disease was tuberculosis of the adrenal gland, but now the majority of patients have adrenal autoantibodies and are thought to have autoimmune adrenalitis. Half of these cases involve other autoimmune endocrine diseases, the resulting syndromes being called polyglandular autoimmune (PGA) syndromes.
Secondary adrenocortical insufficiency, such as in decreased functioning of the pituitary or in prolonged suppression of the pituitary by exogenous glucocorticoid therapy, results in decreased ACTH and hypofunctioning of the adrenal. This produces symptoms similar to those of Addison's disease, such as weakness and weight loss. In contrast to the case with Addison's dis- ease, secretion of aldosterone in patients with secondary adrenocortical insufficiency is normal, because aldosterone production is not controlled by the pituitary gland. Therefore these patients do not develop symptoms of aldosterone deficiency such as volume depletion, hypotension, hyperkalemia, or hyponatremia. Additionally, because ACTH levels are not elevated, there is no hyperpigmentation.
A 41-year-old woman presents with anorexia and weight loss. She has a recent medical history of candida infection of her skin. Physical examination reveals a slightly decreased blood pressure along with increased skin pigmentation. Laboratory examination reveals a low cortisol with increased ACTH. After further workup the diagnosis of adrenal cortical failure is made and a defect in the autoimmune regulator gene is found. Which one of the following abnormalities is most closely associated with this woman's disorder?
a. Hashimoto's thyroiditis
b. Diabetes mellitus
c. Ectodermal dystrophy
d. Parathyroid hyperplasia
e. Pituitary adenoma
c. Ectodermal dystrophy
In 1855, when Thomas Addison first described primary adrenal insufficiency, the most common cause was tuberculosis of the adrenal gland. Now the majority of patients have adrenal autoantibodies and are thought to have autoimmune Addison's disease. Autoimmune adrenalitis may occur by itself (isolated autoimmune Addison's disease) or it may occur with other autoimmune endocrine diseases. Two major patterns of autoimmune poly-endocrine syndromes have been described. In addition to autoimmune adrenitis, patients with autoimmune polyendocrine syndrome type 1 (APS1) have chronic mucocutaneous candidiasis and abnormalities of the skin, nails, and teeth (ectodermal dystrophy). APS1 is also known as APECED (autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy). In addition patients have other autoimmune disorders including autoimmune hypoparathyroidism, idiopathic hypogonadism, and pernicious anemia. APS1 results from mutations of the autoimmune regulator (AIRE) gene, the product of which is expressed primarily in the thymus. Autoimmune polyendocrine syndromes type 2 (APS2) is not associated with candidiasis, ectodermal dysplasia, or autoimmune hypoparathy- roidism. Instead, autoimmune adrenalitis is present with autoimmune thyroiditis (Hashimoto's thyroiditis) or type 1 diabetes mellitus.
Finally, do not confuse autoimmune polyendocrine syndromes with multiple endocrine neoplasia (MEN). Hyperplasia of the parathyroid glands is seen with both type I and type II MEN, while neoplasms of the anterior pituitary are seen with type I MEN only.
A 35-year-old man who presents with a neck mass is found to have a serum calcium level of 11.8 mg/dL and periodic elevation of his blood pressure. Extensive workup reveals the presence of a medullary carcinoma of the thyroid, a pheochromocytoma, and hyperplasia of the parathyroid glands. Which of the following is the most likely diagnosis?
a. Multiple endocrine neoplasia syndrome type 1
b. Multiple endocrine neoplasia syndrome type 2A
c. Multiple endocrine neoplasia syndrome type 2B
d. Polyglandular syndrome type I
e. Polyglandular syndrome type II
b. Multiple endocrine neoplasia syndrome type 2A
Combinations of neoplasms affecting different endocrine organs in the same patient are referred to as multiple endocrine neoplasia (MEN) syndromes. There are several types of MEN syndromes. Patients with type 1 MEN syndrome (Wermer's syndrome) have pituitary adenomas, parathyroid hyperplasia (or adenomas), and neoplasms of the pancreatic islets. The latter most commonly are gastrinomas, which secrete gastrin and produce Zollinger-Ellison syndrome. Type 2A MEN syndrome (Sipple's syndrome) is characterized by the combination of medullary carcinoma of the thyroid, pheochromocytoma of the adrenal medulla, and hyper-parathyroidism. MEN type 2B syndrome (also known as type 3) is associated with medullary carcinoma of the thyroid, pheochromocytoma of the adrenal medulla, and multiple mucocutaneous neuromas.
In contrast to the MEN syndromes, combinations of autoimmune diseases affecting different endocrine organs are called polyglandular syndromes. There are several types of polyglandular syndromes. Patients with type I polyglandular autoimmune syndrome have at least two of the triad of Addison's disease, hypoparathyroidism, and mucocutaneous candidiasis. Type II polyglandular syndrome (Schmidt's syndrome) is not associated with either hypoparathyroidism or mucocutaneous candidiasis, but instead is associated with autoimmune thyroid disease (Hashimoto's thyroiditis) and insulin-dependent diabetes mellitus.
A 34-year-old woman presents with recurrent episodes of severe headaches, palpitations, tachycardia, and sweating. A physical examination reveals her blood pressure to be within normal limits; however, during one of these episodes of headaches, palpitations, and tachycardia, her blood pressure is found to be markedly elevated. Workup finds a small tumor of the right adrenal gland. Which of the following is most likely to be increased in the urine of this individual?
a. Acetone
b. Aminolevulinic acid (ALA)
c. Hydroxy-indoleacetic acid (HIAA)
d. N-formiminoglutamate (FIGlu)
e. Vanillylmandelic acid (VMA)
e. Vanillylmandelic acid (VMA)
Tumors of the adrenal medulla include pheochromocytomas, ganglioneuromas, and neuroblastomas. Pheochromocytomas are composed of cells that contain membrane-bound, dense-core neurosecretory granules and have high cytoplasmic levels of catecholamines. Secretion of these catecholamines produces the characteristic symptoms associated with pheochromocytomas, such as hypertension, palpitations, tachycardia, sweating, and glucose intolerance (diabetes mellitus). Pheochromocytomas are associated with the urinary excretion of catecholamines or their metabolic breakdown products. The catecholamines include dopamine, norepinephrine, and epinephrine. These catecholamines are broken down by two enzymes, catecholamine orthomethyltransferase (COMT) and monoamine oxidase (MAO), into homovanillic acid, normetanephrine, metanephrine, or vanillylmandelic acid (VMA). Any of these metabolic products may be found in the urine of patients with pheochromocytomas; however, VMA is most common. The best screening tests are 24-h urinary metanephrine and VMA levels. Pheochromocytomas have been called the "10% tumor" as 10% are malignant, 10% are multiple (bilateral), 10% are extra-adrenal, 10% calcify, and 10% are familial. These familial tumors are associated with neurofibromatosis, MEN 2A, or MEN 2B.
A 2-year-old boy presents with repeated viral and fungal infections and tetany. Workup reveals hypocalcemia and a marked impairment of cell-mediated immunity resulting from an absence of T cells. Because of these signs and symptoms, the diagnosis of DiGeorge's syndrome is made. Considering this diagnosis, the absence of T cells is a direct result of the failure of which embryonic structure to develop?
a. Third pharyngeal pouch
b. Fourth pharyngeal pouch
c. Fifth pharyngeal pouch
d. Ultimobranchial body
e. Foramen cecum
b. Fourth pharyngeal pouch
The branchial apparatus consists of the branchial clefts (ectoderm), the branchial arches (mesoderm and neural crest), and the branchial (pharyngeal) pouches (endoderm). The dorsal wings of the third pouch develop into the inferior parathyroid glands; the ventral wings of the third pouch develop into the thymus; the fourth pouch develops into the superior parathyroids; and the fifth pouch develops into the ultimo- branchial bodies, which in turn give rise to the C cells of the thyroid. DiGeorge's syndrome results from failure of the third and fourth pharyngeal pouches to develop. This abnormality is associated with tetany and an absence of T cells. The tetany results from the hypocalcemia caused by the lack of the parathyroid glands, while the absence of T cells is caused by the lack of the thymus gland.
A 57-year-old woman presents with difficulty swallowing, drooping eyelids, and double vision. Workup finds a mass in the anterior mediastinum. Biopsies from this mass reveal thymus tissue having scattered reactive lymphoid follicles with germinal centers. Which of the following is the most likely diagnosis?
a. Malignant thymoma
b. Thymic carcinoma
c. Thymic hyperplasia
d. Thymic hypoplasia
e. Thymic lymphoma
c. Thymic hyperplasia
The thymus, derived from the third pair of pharyngeal pouches and inconsistently from the fourth pair, is divided into an outer cortex and an inner medulla and is composed of lymphocytes and epithelial cells. The lymphocytes are mainly T cells, which are immature (thymocytes) in the cortex and are mature in the medulla, where they have phenotypic characteristics of peripheral blood T lymphocytes. The epithelial cells are mainly located in the medulla, forming Hassall's corpuscles. The thymus normally has a few neuroendocrine cells, which may give rise to carcinoid tumors or small cell car- cinoma, and a few myoid cells, which are similar to striated muscle cells and may play a role in the autoimmune pathogenesis of myasthenia gravis. The appearance of lymphoid follicles with germinal centers is abnormal and is diagnostic of thymic hyperplasia.
A 51-year-old woman presents with problems seeing and drooping eyelids. She had been diagnosed 5 years prior as having lupus. A chest x-ray reveals a mass in the anterior mediastinum, which is confirmed by a CT scan. Surgical exploration finds a well-encapsulated tumor. No evidence of invasion is seen. The mass is resected, and histologic sections reveal scat- tered lymphocytes within a diffuse proliferation of spindle-shaped cells. Which of the following is the cell of origin of this tumor?
a. Epithelial cells of the thymus
b. Fibroblasts of the mediastinal mesenchyme
c. Follicular cells of ectopic thyroid tissue
d. Immature T lymphocytes of the thymus
e. Mesothelial cells of the mediastinal mesothelium
a. Epithelial cells of the thymus
Thymomas are tumors arising from thymic epithelial cells and are among the most common mediastinal neoplasms, especially in the anterosuperior mediastinum. Histologic sections reveal a proliferation of spindle-shaped cells. There is a scanty or rich lymphocytic infiltrate of T cells, which are not neoplastic, although their size and prominent nucleoli may cause histologic confusion with lymphoma. About 90% of thymomas are benign and occur at a mean age of 50 years. They are very rare in children. They may be asymptomatic or may cause pressure effects of dysphagia, dyspnea, or vena cava compression. Associated systemic disorders include myasthenia gravis, hematologic cytopenias, collagen vascular disease (lupus), and hypogammaglobulinemia. Malignant thymomas show infiltration and capsular invasion plus pleural implants or distant metastasis.
In contrast, the other type of cell found in the thymus, T lymphocytes, give rise to T-cell lymphoblastic lymphomas. Finally, recall that fibroblasts give rise to fibromas or fibrosarcomas, and mesothelial cells give rise to benign or malignant mesotheliomas.
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