A 64-year-old man with a history of hypertension and a 30-pack-year smoking history presents with unrelenting abdominal pain and constipation. He also endorses nausea and his wife reports that he has exhibited subtle signs of mental deterioration. He has a temperature of 36.8°C, blood pressure of 118/72 mmHg, heart rate of 98 beats per minute, respiratory rate of 18 breaths per minute, and oxygen saturation of 96% on room air. Physical examination is unremarkable and laboratory studies reveal the following:
What additional laboratory value do you expect to find with this patient’s condition?
Increased levels of parathyroid hormone–related protein. The patient in this question presents with classic features of hypercalcemia (polyuria, nausea, vomiting, polydipsia, constipation, and cognitive dysfunction). His serum calcium is elevated with a suppressed serum parathyroid hormone (PTH) level. In addition, the history of extensive smoking gives an important clue that hypercalcemia of malignancy should be highly considered here. With hypercalcemia of malignancy, serum calcium levels are much more elevated than in patients with primary hyperparathyroidism (the most common cause of hypercalcemia, but in this case not the diagnosis given that serum PTH is suppressed with this patient). (B) In hypercalcemia of malignancy, osteolytic metastases contribute to the markedly elevated calcium level, but you would also expect secretion of parathyroid hormone–related protein (PTH-rP), in addition to increased interleukin-6 levels. (A) Increased angiotensin-converting enzyme (ACE) blood levels is often seen in sarcoidosis; however, this patient has low 1,25-dihydroxyvitamin D levels and you would expect elevated levels in sarcoidosis due to the increased conversion in granulomatous tissue. Also, calcium is usually not as high in sarcoidosis. (C) Decreased urine calcium levels would be found in another cause of hypercalcemia called familial hypercalcemia hypocalciuria; however, this would be accompanied by high to normal PTH levels (and this patient has suppressed serum PTH levels).
A 32-year-old woman with a history of endometriosis presents with weight loss, diarrhea, and increased appetite for the past 6 weeks. She has a temperature of 37°C, blood pressure of 132/88 mmHg, heart rate of 75 beats per minute, respiratory rate of 18 breaths per minute, and oxygen saturation of 99% on room air. Physical examination reveals a diffusely large, nontender thyroid gland in addition to the findings seen in the photo below (Figure below). Laboratory studies confirm the diagnosis and the patient opts for treatment with methimazole.
Which of the following adverse effects is important to inform the patient of before beginning treatment with this medication?
Agranulocytosis. The patient in this question has been diagnosed with Graves disease and demonstrates exophthalmos and lid retraction. In addition to methimazole, propylthiouracil is another antithyroid drug that can be used in place of radioactive iodine ablation or thyroidectomy. There are several side effects of propylthiouracil and methimazole, several of which are shared by both drugs and some that are unique to each one. Side effects that are shared by both include skin rash, arthralgias, hepatotoxicity, and agranulocytosis. Methimazole can cause jaundice and is teratogenic in the first trimester. (B, D) Propylthiouracil (PTU) can cause vasculitis and is not preferred over methimazole since it carries a risk of acute liver failure. Of note, PTU is preferred during pregnancy. (A) Hypocalcemia is indeed an adverse effect from thyroidectomy, but the patient in this question opted for medical management over surgery.
A 28-year-old man with a history of type 1 diabetes presents with polydipsia and polyuria for the last 5 weeks. The patient reports that his blood glucose levels have been well controlled on his current insulin regimen. The patient denies tobacco, alcohol, or drug use and has no other past medical history. He has a temperature of 36.8°C, blood pressure of 114/68 mmHg, heart rate of 96 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 98% on room air. The patient reports that he has fasted for the visit and laboratory results reveal the following:
Desmopressin was administered and 30 minutes later the urine osmolality is 432 mOsm/kg.
Which of the following is this patient’s diagnosis?
Central diabetes insipidus. The patient in this question presents with polyuria and polydipsia with a normal serum glucose level. Given the patient’s hypernatremia, low urine osmolality, and elevated serum osmolality, the patient likely has diabetes insipidus (DI) and it now remains to distinguish between central and nephrogenic DI.
(A) Primary polydipsia is not the answer here because in primary polydipsia you would expect hyponatremia given that the increased water consumption in primary polydipsia overwhelms the capability of the kidneys to excrete the water. (D) SIADH is incorrect for the same reason—you would expect hyponatremia and this patient has hypernatremia (sodium >145 mEq/L). Central DI occurs when the pituitary gland does not secrete sufficient ADH. Nephrogenic DI occurs when the nephrons themselves show resistance to ADH (but ADH levels will be normal because the pituitary gland is functionally intact). In nailing the diagnosis, the patient must first engage in a water deprivation test for at least 2 hours. If the urine osmolality is >600 mOsm/kg at the conclusion of the test, then the diagnosis is likely primary polydipsia since the patient is able to concentrate urine without water intake. If the urine is still dilute (<600 mOsm/kg) at the end of the water deprivation test, then desmopressin (synthetic vasopressin) is administered and urine osmolality is monitored. If urine osmolality increases, then this proves that pituitary secretion of ADH is deficient and central DI is diagnosed. Nephrogenic DI will have negligible change in urine osmolality since the problem is renal pathology (not the amount of ADH). The patient in this question has a urine osmolality that increased about 400% after desmopressin, establishing the diagnosis as central DI.
A 72-year-old woman presents with bone pain and tenderness in her lower extremities and left clavicle. Review of her chart reveals chronic bone marrow fibrosis with increased bone remodeling, in addition to several episodes of kidney stones (specifically calcium oxalate). Physical examination reveals tenderness to palpation on her lower legs and left midclavicle. Laboratory studies reveal elevated calcium, decreased phosphate, and elevated parathyroid hormone (PTH). X-ray reveals the following:
Which of the following is the diagnosis?
Osteitis fibrosa cystica. The patient in this question has hyperparathyroidism (elevated PTH) and is showing clinical symptoms for osteitis fibrosa cystica, a disease in which cystic bone spaces are filled with brown fibrous tissue. This disease is associated with hyperparathyroidism because PTH first acts on osteocytes and then on osteoclasts, causing calcium to be resorbed from the bone matrix and available in the blood stream (hypercalcemia). PTH also causes decreased phosphate reabsorption in the nephron, which causes decreased blood phosphate levels (hypophosphatemia). Hypercalciuria is yet another sign of hyperparathyroidism, which leads to the formation of calcium oxalate stones. The above figure shows osteosclerosis with greater density at the endplates (rugger jersey spine), which can be seen with hyperparathyroidism.
(A, C) Paget disease of the bone also causes bone pain and involves disorganized bone remodeling, but this disease usually causes misshapen bones and fractures and is typically localized to only a few bones in the body, in contrast with osteoporosis in which typically all the bones in the body are affected. Furthermore, laboratory studies are critical for nailing the diagnosis, since Paget disease of the bone and osteoporosis do not cause changes in calcium, phosphate, and PTH levels (although Paget disease is associated with increased alkaline phosphatase). (B) Osteomalacia involves defective bone mineralization due to vitamin D deficiency in adults, causing decreased calcium levels, which subsequently causes PTH to increase. With the increased secretion of PTH, serum phosphate levels decrease.
A 48-year-old woman presents with weight gain, easy bruisability, and muscle weakness. She has a 30-pack-year history of smoking. She presents with a temperature of 36.8°C, blood pressure of 144/92 mmHg, heart rate of 96 beats per minute, respiratory rate of 16 breaths per minute, and oxygen saturation of 98% on room air. Physical examination reveals the finding seen in the photo below. Laboratory studies are significant for a fasting blood glucose of 310 mg/dL, a 24-hour urine cortisol level of 1,200 μg (normal range, 10 to 100 μg), and a plasma ACTH of 126 pg/mL (normal range, 10 to 60 pg/mL). Twenty-four– hour urine cortisol level is 1,184 μg after high-dose dexamethasone is administered.
Which of the following is the cause of the patient’s symptoms and laboratory findings?
Ectopic ACTH-producing tumor. The patient in this question is presenting with typical symptoms of Cushing syndrome. In addition to weight gain, easy bruisability, and muscle weakness, symptoms include moon facies, truncal obesity, buffalo hump, hyperglycemia, osteoporosis, amenorrhea, and hypertension. Cushing syndrome by definition only signifies increased cortisol levels, so there must be a workup to determine the etiology of the disorder. One must first diagnose Cushing syndrome by initially screening with a 24-hour urine cortisol level. The vast majority of patients with Cushing syndrome have levels greater than 90 μg/24 hours. Once the diagnosis of Cushing syndrome has been made, the etiology must then be determined by measuring plasma ACTH level (elevated ACTH is considered greater than 20 pg/mL). (A) The most common cause of Cushing syndrome is exogenous steroids; however, this will have a low ACTH level due to the steroids negatively inhibiting secretion of ACTH from the pituitary. (B) Likewise, adrenal-related causes of Cushing syndrome such as adrenocortical adenoma will have a decreased ACTH level. Our patient, on the other hand, presents with an elevated ACTH level and so then next step is to distinguish between Cushing disease (increased ACTH secretion from a pituitary adenoma) and ectopic ACTH production, sometimes seen in small cell lung cancer. (D) High-dose dexamethasone will normally suppress urinary cortisol or serum cortisol levels in Cushing disease, but will not suppress cortisol levels in ectopic ACTH production. In this patient, 24-hour urine cortisol levels were not adequately suppressed (defined as suppressing cortisol levels by at least 50%), so ectopic ACTH production (likely small cell lung cancer given the patient’s smoking history) is the diagnosis.
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