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A 42-year-old woman with a history of pernicious anemia comes to the physician complaining of increased anxiety, heart palpitations, heat intolerance, unexplained weight loss, and multiple daily bowel movements. She has not had a period in 4 months. On physical examination, the patient is found to have a goiter, a thyroid bruit, and mild exophthalmos. Laboratory studies show elevated triiodothyronine and free thyroxine levels, and an undetectable thyroid-stimulating hormone. Which of the following is the most likely etiology of this patient’s disease?

Autoimmune stimulation of thyroid-stimulating hormone receptors

This patient presents as a classic case of Graves’ disease. In Graves’ disease, thyroid-stimulating IgG antibodies bind to TSH receptors and lead to thyroid hormone production. This causes glandular hyperplasia and enlargement characteristic of the goiter associated with Graves’ disease. Graves’ disease is the most common cause of thyrotoxicosis. Patients with this condition may have other autoimmune diseases, such as pernicious anemia or type 1 diabetes mellitus, and frequently present with anxiety, irritability, tremor, heat intolerance with sweaty skin, tachycardia and cardiac palpitations, weight loss, increased appetite, fi ne hair, diarrhea, and amenorrhea or oligomenorrhea. Signs include diffuse goiter, proptosis, periorbital edema, and thickened skin on the lower extremities. Laboratory values reveal increased thyroid hormone levels and decreased TSH levels


A certain endocrine disorder can lead to an elevated blood pressure, decreased potassium levels, sodium and water retention, and decreased renin activity. Which of the following is the most likely diagnosis?

Primary hyperaldosteronism

Primary hyperaldosteronism is most commonly caused by an aldosterone-producing adenoma of the adrenal gland. It can also be found in patients with zona glomerulosa hyperplasia. The increased levels of aldosterone lead to hypertension, increased sodium and water retention, and the associated increase in excretion of potassium leading to hypokalemia. Increased blood pressure and aldosterone levels produce negative feedback to the kidneys, resulting in a decreased level of serum renin. Serum renin levels help differentiate between primary hyperaldosteronism, with increased aldosterone and decreased renin levels, and secondary hyperaldosteronism, with increased aldosterone levels and increased renin levels.


A 59-year-old man with no prior medical history presents to the physician with marked hyperglycemia, diarrhea, and weight loss. A CT scan of the abdomen reveals a pancreatic mass. A trial period on an oral hypoglycemic agent has not helped reduce his glucose levels. His physical examination is signifi cant for the rash shown in the image. Which of the following is the most likely diagnosis?


This patient has symptoms of a glucagonoma, a rare glucagonsecreting tumor that can cause hyperglycemia, diarrhea, and weight loss. The hyperglycemia seen in these patients will not respond to oral hypoglycemic agents because of the uncontrolled excess glucagon production that continues despite increased insulin levels. Glucagonomas are also associated with necrolytic migratory erythema, a skin rash consisting of painful, pruritic erythematous papules that blister, erode, and crust over


A 5-year-old girl is brought to the pediatrician by her mother because she has noticed a single soft, nontender mass underneath her daughter’s tongue. The physician reassures the mother that it is a common congenital ectopic anomaly that does not affect the function of the mass or the hormone it secretes. Hypersecretion of this hormone can cause which of the following conditions?


Usually, the thyroid gland develops beneath the tongue, descends along the thyroglossal duct, and eventually resides anterior to the trachea in the neck. Ectopic thyroid tissue may be found anywhere along the course of the duct, including its place of origin: beneath the tongue. This is a common congenital anomaly that does not affect thyroid function, and it should not be removed. Hypersecretion of thyroxine (T4) from the ectopic gland can result in menstrual abnormalities, including amenorrhea and oligomenorrhea.


A 60-year-old patient from an underserved indigent family sees a physician and complains of years of polydipsia, polyuria, polyphagia, and worsening fatigue and weight loss. Urinalysis reveals severe proteinuria, and a renal biopsy is ultimately performed, with a typical histologic section shown in the image. Which of the following histological fi ndings is apparent in the renal tissue?

Nodular glomerulosclerosis

The vignette is a classic case of a patient with type 2 diabetes mellitus: polydipsia, polyuria, and polyphagia in an individual >40 years old. This condition is due to increased resistance to insulin. The image shows nodular glomerulosclerosis, also known as Kimmelstiel-Wilson glomerulosclerosis. This represents the accumulation of nodules in the mesangial matrix, which is pathognomonic for diabetes mellitus. Kidneys of diabetic patients also show increased basement membrane thickness and diffuse mesangial matrix proliferation


A 34-year-old man with moderately severe ulcerative colitis has been taking oral prednisone for 4 months. Which of the following symptoms is the most likely adverse effect of this drug

Diabetes mellitus

This patient is at risk for prednisone-induced Cushing’s syndrome. Cushing’s syndrome is associated with diabetes mellitus, which can be an adverse effect of chronic corticosteroid use owing to decreased glucose tolerance and the counterregulatory action of the hormone. Glucocorticoids increase the glucose production by the liver in part by stimulating gluconeogenesis, and also by stimulating proteolysis in the skeletal muscle and releasing glucogenic amino acids into the vasculature.


A 45-year-old man with type 2 diabetes mellitus undergoes a neurologic examination. The patient is unable to sense the vibration produced by a tuning fork placed on his big toe. Which of the following receptors is most likely affected in this patient?

Pacinian corpuscle

The sensory receptors responsible for transducing the sensation of vibration, pressure, and tension are the large, encapsulated pacinian corpuscles, which are located in the deeper layers of the skin, ligaments, and joint capsules. They can be distinguished histologically by their onionlike appearance on cross section. This patient is presenting with one of the complications of diabetes, neuropathy, and since pacinian corpuscles are responsible for transducing vibratory stimuli, it is these receptors that are involved in this patient’s presentation.


. A 53-year-old woman with newly diagnosed type 2 diabetes presents to the emergency department complaining of vomiting, severe headache, dizziness, blurry vision, and diffi - culty breathing. She says that she had been at a cocktail party when the symptoms began. Her skin is notably fl ushed on physical examination. Which of the following medications is responsible for this reaction?


This patient had a disulfi ramlike reaction after drinking alcohol at a cocktail party. Of the diabetes medications listed, only tolbutamide is associated with causing a disulfi ramlike reaction after alcohol consumption. Tolbutamide is a sulfonylurea antidiabetic agent. Sulfonylureas lower blood glucose in patients with type 2 diabetes by directly stimulating the release of insulin from the pancreas. They do this by binding to the sulfonylurea receptor on the β islet cell, leading to the inhibition of potassium ion effl ux, cell depolarization, subsequent opening of voltagegated calcium channels, and calcium infl ux, which triggers the release of preformed insulin. Other drugs known to cause a disulfi ramlike reaction include metronidazole, quinacrine, griseofulvin, and chloramphenicol, as well as some cephalosporins including cefamandole and cefoperazone


A 25-year-old man comes to the emergency department after experiencing tremors. He appears visibly anxious and relates a recent history of sweats, nausea, vomiting, and lightheadedness. Laboratory studies show a blood glucose level of 50 mg/dL. An abdominal CT scan shows a 1.5-cm mass in the head of the pancreas. Surgical resection of this mass will necessitate ligation of branches from which of the following vascular structures?

The gastroduodenal and superior mesenteric arteries

The head of the pancreas and the duodenum share a dual blood supply from the gastroduodenal artery, a branch of the celiac trunk. This artery supplies the anterior and posterior superior pancreaticoduodenal arteries as well as the superior mesenteric artery, which supplies the anterior and posterior inferior pancreaticoduodenal arteries. Therefore, to resect any portion of the duodenum or the head of the pancreas, branches from both the gastroduodenal and superior mesenteric arteries must be ligated.


A 36-year-old woman presents to the physician with amenorrhea. She reports an increase in her ring and shoe sizes over the past year, increased sweating, and increased fatigue. Physical examination shows a blood pressure of 150/90 mm Hg and coarse facial features with mild macroglossia. Which of the following is most appropriate for this patient?


This patient presents with acromegaly, the clinical syndrome that is a result of excessive growth hormone (GH) secretion in adults (after closure of the physes). Octreotide is a somatostatin analog that acts at the anterior pituitary to suppress GH secretion, and is used in the treatment of acromegaly. Surgical and radiotherapeutic approaches are also an option, depending on the etiology. Somatostatin is normally secreted by the hypothalamus to help regulate basal GH secretion.


A 23-year-old man comes to the physician because of intermittent severe headaches, anxiety, and heart palpitations. While he has no signifi cant medical history, his uncle had similar symptoms. When probed for a deeper family history, he says that his mother and two cousins have had their thyroids removed. Which of the following conditions most likely accounts for the clinical scenario?


The headache, anxiety, and palpitations suggest an excess of catecholamines stimulating the sympathetic nervous system. A pheochromocytoma may be suspected, and since there appears to be familial involvement, the related multiple endocrine neoplasia (MEN) syndromes should also be considered. MEN type II (used to be called type 2a) consists of medullary thyroid carcinoma (MTC), pheochromocytoma, and tumors of the parathyroid. MEN type III (used to be type 2b) usually includes MTC, pheochromocytoma, and neuromas instead of parathyroid tumors. It is therefore likely that this patient’s relatives had their thyroids removed due to MTC. One could further differentiate the two types by looking for neuromas on the lips, tongue, or eyelids or in the gastrointestinal tract causing constipation/diarrhea, or for hyperparathyroidism manifesting in bradycardia, hypotonia, fatigue, and bone pain.


Growth hormone is essential to normal human growth and development, and its secretion is tightly regulated via a feedback control system involving the hypothalamus, the pituitary gland, and the peripheral tissues. Which of the following is a stimulus for the secretion of growth hormone?


In addition to being necessary to normal human growth and development, GH is critical in the stress response to starvation. GH is released in response to hypoglycemia and acts directly to decrease glucose uptake by cells and increase lipolysis, resulting in an increase in blood sugar levels


The product of the cells shown in this image induces a rise in serum calcium levels. Which of the following types of cells are indicated by the arrows in this image?

Parathyroid chief cells

Parathyroid chief cells are small, pale cells with round central nuclei. These cells secrete parathyroid hormone, which raises serum calcium levels in three ways: (1) it acts directly on bone to increase osteoclastic resorption; (2) it acts directly on the kidney to increase resorption of calcium and inhibit resorption of phosphate; and (3) it promotes gastrointestinal absorption of calcium via increased levels of activated vitamin D.


A 66-year-old man with chronic cough, dyspnea, and a 50-pack-year history of cigarette smoking comes to the clinic after noticing blood in his sputum. He says he feels lethargic and has lost 18 kg (40 lb) over the past 3 months with no changes in diet or exercise. Laboratory studies show a serum sodium level of 120 mEq/L. While awaiting CT, the patient suffers a seizure and is rushed to the emergency department. Which of the following is most likely to be elevated in this patient?


This vignette is most consistent with a syndrome of inappropriate secretion of ADH due to a lung neoplasm. ADH is secreted by the posterior pituitary and stimulates the expression of aquaporins in the renal collecting ducts, resulting in transport of water into the renal medulla from the ductal lumen and hence water retention in the kidneys. When levels of this hormone are inappropriately elevated, excessive water retention results in hyponatremia, which can lead to seizures. ADH can be produced ectopically in the setting of malignancy, classically by small cell lung cancer.


A 65-year-old woman comes to her primary care physician complaining of progressive weakness and fatigue. On further questioning, she notes a recent weight gain and constipation as well as constant subjective chills. Physical examination shows a moderate nontender goiter. A biopsy shows a lymphocytic infi ltrate. Which of the following best describes this patient’s thyroid-stimulating hormone (TSH) and thyroid hormone levels relative to normal baseline values?

C. Increased thyroid-stimulating hormone and decreased total thyroxine and free thyroxine. 

The vignette describes a classic history for hypothyroidism caused by Hashimoto’s thyroiditis. This primary hypothyroidism is characterized by reduced secretion of thyroid hormone, resulting in decreased levels of free and total T4 and increased levels of TSH due to the absence of negative feedback by T4


A 27-year-old woman presents to a new physician with muscle cramping and spasm. On physical examination, the physician notes shortened fourth and fi fth metacarpals and metatarsals, short stature, a round face, and abnormal teeth. Her facial muscles twitched when her facial nerve was tapped, and her wrist twitched with the use of a blood pressure cuff. Laboratory studies show a decreased serum calcium level and a signifi cantly elevated parathyroid hormone level. There is no evidence of renal disease, thus decreasing the likelihood of renal osteodystrophy. Which of the following is the most common mode of inheritance of this patient’s disease?

Autosomal dominant

This patient had pseudohypoparathyroidism. In all forms of pseudohypoparathyroidism, there is a defect in the peripheral organ response to PTH, leading to increased PTH levels. There are several types of pseudohypoparathyroidism, which vary in clinical presentation. This is an autosomal dominant disease, and penetrance is variable. Pseudohypothyroidism is caused by kidney unresponsiveness to PTH.


A 43-year-old woman presents with fatigue, a 4.5-kg (9.9-lb) weight gain over the past 3 months, cold intolerance, hair loss, and con-centration problems. Physical examination is signifi cant for dry, coarse skin and bradycardia. She states that she had some slight swelling of her lower neck several months ago, which resolved without treatment. Results of antithyroglobulin antibody and antinuclear antibody tests are negative, but a thyroid peroxidase antibody test is positive. What other autoimmune diseases will this patient most likely have?

Type 1 diabetes mellitus and celiac disease

This patient has Hashimoto’s thyroiditis, an autoimmune disorder in which patients have antibodies attacking thyroglobulin, thyroid peroxidase, or another part of the thyroid gland or thyroid hormone synthesis pathway. Patients with Hashimoto’s thyroiditis have a 20 times greater prevalence of celiac disease and type 1 diabetes mellitus than the general population.


A 45-year-old man comes to his primary care physician complaining of back pain. On questioning, the patient indicates a recent history of polyuria, polydipsia, hypertension, and weight gain. X-ray of the spine shows an L4-L5 compression fracture. Which of the following is most likely to be elevated in this patient?


This patient’s recent history of hyperglycemic symptoms, hypertension, and weight gain are all consistent with a diagnosis of Cushing’s syndrome, which is characterized by hypercortisolemia. This leads to exaggeration of the physiologic effects of cortisol, such as hyperglycemia and insulin resistance, immune suppression, and hypertension (a consequence of salt retention due to secondary elevation of aldosterone). One result of this syndrome is osteoporosis, which is caused by increased bone resorption in response to an elevated serum cortisol level. Vertebral compression fractures are common manifestations of osteoporosis


A 60-year-old woman with a history of type 2 diabetes mellitus comes to the clinic for a follow-up examination after being placed on a new agent to help her achieve tighter glycemic control. She complains that she has suffered occasional abdominal cramps and diarrhea, adding that she has recently been experiencing increased fl atulence, which has become an embarrassing nuisance. Which of the following agents best accounts for this patient’s complaints?


Acarbose is an α-glucosidase inhibitor that decreases the hydrolysis and absorption of disaccharides and polysaccharides at the intestinal brush border, thereby reducing postprandial hyperglycemia. This drug can be used as monotherapy or in combination with oral hypoglycemic medications in the management of type 2 diabetes mellitus. Acarbose commonly causes gastrointestinal adverse effects that include abdominal cramps, diarrhea, and fl atulence.


A 42-year-old man comes to the physician with loss of vision in the lateral periphery on both sides as well as decreased libido. On physical examination his features appear coarser and larger than in a photograph taken 1 year ago, and he states that his glove size and shoe size have changed over the past year as well. His MRI is shown in the image. Which of the following is the most likely diagnosis?

Growth hormone-secreting pituitary adenoma

Bitemporal hemianopsia (due to compression of the optic nerves at the chiasm) and diminished libido are common presenting symptoms of pituitary tumors in men. The MRI shows a pituitary adenoma. When these adenomas become large enough, they exert mass effect on the second cranial nerves at the chiasm. GH-secreting pituitary adenomas are slow-growing and often go undiagnosed for several years. GH hypersecretion is associated with acromegaly, resulting in bone overgrowth with increased hand and foot size, soft tissue swelling, oily skin, and proximal muscle weakness.


A 39-year-old woman is seen by a physician because of a lump in the front of her neck. Physical examination reveals a swollen thyroid gland. A biopsy of the enlarged but painless thyroid gland is found to contain psammoma bodies and thin projections of epithelium surrounding a fi brovascular core. The nuclei of many cells are optically clear. Which of the following risk factors is most commonly associated with her diagnosis?

Prior radiotherapy to the head or neck

Papillary thyroid carcinoma is the most common type of thyroid cancer. It is always distinguished by its fingerlike projections of epithelium surrounding a central fibrovascular core, calcifi ed spheres (psammoma bodies), optically clear “Orphan Annie” nuclei, and molding of the nuclei. Patients often have a prior history of radiation to the head or neck. Papillary thyroid carcinoma carries a better prognosis than the other forms of thyroid cancer.


Glucocorticoids are important in the treatment of infl ammatory diseases; however, their use is associated with many adverse effects on multiple systems. The utility of glucocorticoids has to be weighed against the patient’s ability to withstand the problems that are likely to arise. High-dosage glucocorticoid treatment can result in which ECG changes?

Appearance of U wave

Acute high-dosage glucocorticoid treatment can cause a change in electrolyte levels by their cross-reactivity to the mineralocorticoid receptors, thus causing sodium retention and potassium depletion. Hypokalemia is manifested on ECG as a U wave, which is a small wave that follows the T wave.


Surgery is planned to excise a hyperfunctioning adrenal adenoma from a patient with primary hyperaldosteronism. On CT scan of the abdomen, the adenoma is visible as a 4-cm mass just superior to the right kidney. In order to immediately relieve the patient’s hyperaldosteronism, the surgeon must fi rst ligate the primary venous drainage of the tumor. The primary venous drainage fl ows directly into which of the following structures?

Inferior vena cava

The right adrenal gland is drained via the right adrenal vein, which fl ows directly into the inferior vena cava (IVC). Thus, a right-sided hyperfunctioning adrenal adenoma is drained via the right adrenal vein into the IVC. In contrast, the left adrenal gland is drained via the left adrenal vein into the left renal vein, which then fl ows into the IVC.


A 54-year-old man with a history of smoking and lung cancer develops hypercalcemia. He is enrolled in a research study to assess the effi - cacy of a new synthetic agent to treat this condition. After several days of treatment, he reports persistent numbness and tingling around his mouth. Physical examination is signifi cant for facial spasm when the jaw is tapped and carpal spasm when the blood pressure cuff is infl ated. Which of the following was most likely used to treat his hypercalcemia?


This vignette describes a patient with classic symptoms and signs of hypocalcemia, including Chvostek’s sign (facial spasm) and Trousseau’s sign (carpal spasm). All of these fi ndings can be attributed to the physiologic effects of calcitonin. Calcitonin is normally secreted in response to elevated levels of serum calcium and causes decreased bone resorption of calcium, resulting in lower calcium levels.


A 34-year-old African-American woman presents to the physician with abdominal cramping that worsens during her menstrual period. The patient also says that her periods often last for more than 7 days. An ultrasound study shows multiple masses on the patient’s uterus. Which of the following immunohistochemical stains would be the most appropriate for diagnosing this patient’s condition?


This vignette describes leiomyomas, or fi broids, which are most often seen in African- American women. These tumors are benign and usually present with menstrual pain and menorrhagia (increased bleeding). They are estrogen-sensitive, increasing in size during pregnancy and decreasing with menopause. As their name suggests, leiomyomas are composed of muscle fibers; thus, the appropriate stain is desmin.


A 34-year-old woman goes to her primary care physician complaining of a recent feeling that “her heart was racing” and visual changes. During the interview, the physician notices that the patient is clearly anxious. During the review of systems, the patient reveals a recent unintentional 4-kg (8.8-lb) weight loss. On physical examination, the physician notes that the patient is tachycardic and has 2+ nonpitting edema in her lower extremities. Which of the following is the most likely etiology of this disease?

Autoantibodies to the thyroid-stimulating hormone receptor

This patient has Graves’ disease, an autoimmune disorder resulting from IgG-type autoantibodies to the thyroid-stimulating hormone receptor. The three classic findings associated with Graves’ disease are hyperthyroidism, ophthalmopathy, and dermopathy/pretibial myxedema.


An 18-year-old woman is referred to a specialist because her periods have stopped. She reports occasional bouts of nausea, vomiting, and generalized weakness. Her blood pressure is 160/99 mm Hg; laboratory studies show a serum K+ level of 2.2 mEq/L. This patient suffers from a condition that affects the production of two of the three adrenal hormones, leaving only one functioning hormone. In which area of the adrenal gland is this one hormone produced?

Zona glomerulosa

17-α-Hydroxylase deficiency, a form of congenital adrenal hyperplasia, is characterized by defi cits in glucocorticoid and sex steroid synthesis. This is coupled with increased mineralocorticoid production due to the increased fl ow of precursors, such as pregnenolone and progesterone, through mineralocorticoid-yielding pathways. The resultant low serum cortisol and sex steroid levels with elevated mineralocorticoid levels manifest clinically with hypertension, hypokalemia, and a female phenotype with no sexual maturation. Aldosterone is produced in the zona glomerulosa. Aldosterone synthesis requires 21-β-hydroxylase but not 17-α-hydroxylase. Remember the mnemonic “Salt, Sugar, and Sex” for the layers of the adrenal cortex and their respective products


A 66-year-old man comes to the emergency department because of weight loss, hypotension, and hyperpigmented skin. Laboratory tests show decreased serum levels of sodium, chloride, and cortisol, but increased serum levels of potassium and ACTH. Additionally, the urinary level of 17-hydroxypregnenolone is decreased. Which of the following most likely explains this patient’s symptoms and laboratory values?

Autoimmune destruction of the adrenal glands

This patient’s laboratory values are consistent with Addison’s disease, a primary defi ciency of aldosterone and cortisol due to adrenal hypofunction. This condition leads to hypotension and skin hyperpigmentation. Lack of aldosterone production results in the electrolyte imbalance seen in this patient’s lab values: low aldosterone reduces renal sodium reabsorption and potassium secretion, resulting in low serum sodium and high serum potassium levels with hypotension. ACTH levels increase due to the loss of negative feedback from low cortisol levels. Adrenal atrophy can be due to a number of causes, including autoimmune destruction, infection, and adrenal hemorrhage. Importantly, adrenal atrophy reduces the hydroxylation of pregnenolone by 17-α-hydroxylase present in the adrenals. This is the cause of reduced urinary 17-hydroxypregnenolone


The predominant cells in this photomicrograph from the adrenal medulla secrete which of the following hormones into the bloodstream?


Chromaffin cells are neuroendocrine cells derived from the embryonic neural crest. They are found in the medulla of the adrenal gland and in sympathetic nervous system ganglia. Chromaffi n cells of the adrenal medulla are innervated by the splanchnic nerve and secrete epinephrine, norepinephrine, and enkephalin into the bloodstream. They derive their name from their ability to be visualized by staining with chromium salts. These cells have large nuclei and are strongly basophilic, in contrast to the more eosinophilic zona reticularis cells. They contain little endoplasmic reticulum and no stored lipid. Norepinephrine-secreting cells are distinguished from epinephrine-secreting cells by virtue of having dense core granules and a more strongly positive chromaffi n reaction.


A researcher investigating the action of thyroid hormones wants to develop an assay to analyze the activity of this hormone in various tissues. Which of the following strategies would be most effective in determining the level of activity of these hormones in a tissue sample?

Assessing Na+/K+-ATPase mRNA levels

Thyroid hormones act via a nuclear hormone receptor. On binding with its ligand, the receptor translocates from the cytoplasm to the cell nucleus, and the ligand-receptor complex acts as a transcription factor. This results in gene transcription and new protein synthesis. This answer is the only one that involves assessment of gene transcription, and thus represents the only selection that refers to a nuclear hormone receptor mechanism. Furthermore, an important function of thyroid hormones is increasing basal metabolic rate, which is mediated by increasing Na+/K+- ATPase expression and activity. Other hormones that act through nuclear steroid hormone receptors include cortisol, aldosterone, vitamin D, testosterone, estrogen, and progesterone.