A 73-year-old woman with a history of type 2 diabetes and hypertension presents with rapid breathing, nausea, abdominal pain, and diarrhea. Her blood glucose has been well controlled and a rapid bedside blood glucose test reveals a level of 106 mg/dL. She informs you that 3 weeks ago she was taken off an oral antidiabetic medication due to several episodes of hypoglycemia and started on another oral antidiabetic medication, but she cannot recall the name. She has a temperature of 36.8°C, blood pressure of 120/78 mmHg, heart rate of 96 beats per minute, respiratory rate of 28 breaths per minute, and oxygen saturation of 96% on room air.
Based on clinical history and physical examination, which of the following do you expect on arterial blood gas?
Metabolic acidosis with high anion gap. The patient in this question is presenting with hyperventilation due to an underlying acid–base change. This question tests the student’s knowledge of side effects of oral antidiabetic medications. Given the patient’s normal blood glucose level, it is very unlikely that she is suffering from DKA; however, she informs you that she recently changed medications and now has abdominal pain and diarrhea. These are likely side effects from metformin (a biguanide medication that inhibits hepatic gluconeogenesis). Given the previous medication caused hypoglycemia, she was likely taking a sulfonylurea (which increases insulin secretion and therefore can cause hypoglycemia). Metformin can cause lactic acidosis, one of the several causes of high anion gap metabolic acidosis (others include methanol, uremia from chronic renal failure, DKA, propylene glycol, isoniazid, ethylene glycol, and salicylates). This would explain her hyperventilation because she is compensating for a low bicarbonate level. Other side effects of metformin include metallic taste and weight loss. Metformin should not be given in patients with renal insufficiency or liver disease. A, B, D, and E are other acid–base abnormalities that have completely different etiologies than lactic acidosis. Of note, metabolic acidosis with a normal anion gap is typically associated with chronic diarrhea, renal tubular acidosis (RTA), and ureterosigmoidostomy.
A 53-year-old man with a history of thyroid medullary cancer presents with several episodes of a “racing heart,” palpitations, diaphoresis, and headaches. He has a temperature of 37.8°C, blood pressure of 158/96 mmHg, heart rate of 96 beats per minute, respiratory rate of 18 breaths per minute, and oxygen saturation of 96% on room air. Urine test reveals small amounts of normetanephrine and metanephrine.
Which of the following, if present in this patient, would establish the diagnosis as multiple endocrine neoplasia (MEN) type 2B?
Mucocutaneous neuromas. The patient in this question is presenting with signs and symptoms of pheochromocytoma, a neuroendocrine tumor of the adrenal medulla that secretes high amounts of catecholamines. Given that he has a history of thyroid medullary cancer, the MEN syndromes must be considered highly on the differential diagnosis. Both MEN type 2A and MEN type 2B include thyroid medullary cancer and pheochromocytoma. However, only MEN type 2B includes mucocutaneous neuromas as one of its characteristic diagnoses. MEN type 2B also is characterized by marfan-like body habitus and ganglioneuromatosis of the colon. (A) Parathyroid hyperplasia is seen in MEN type 1 and MEN type 2A, but not in MEN type 2B. (C) Pituitary adenoma is seen in MEN type 1, but not in the other MEN syndromes. (D) Proptosis is often seen in Graves disease, the most common cause of hyperthyroidism. This information is summarized in Table below.
Findings in the MEN Syndromes:
A 23-year-old man with a history of type 1 diabetes presents with nausea, vomiting, abdominal pain, and rapid breathing. His girlfriend reports that he has a “nail polish” odor. The symptoms appeared 24 hours ago and have rapidly worsened. Two weeks ago he was treated for pneumonia. He has a temperature of 37.8°C, blood pressure of 92/58 mmHg, heart rate of 104 beats per minute, respiratory rate of 26 breaths per minute, and oxygen saturation of 94% on room air. Physical examination reveals decreased skin turgor, dry axillae and oral mucosa, and low jugular venous pressure. Laboratory results reveal the following:
Arterial blood gas
Treatment with IV fluids and insulin is initiated.
Which of the following should NOT be used to monitor response to therapy?
Urine ketones via nitroprusside test. The patient in this question presents with signs and symptoms of DKA, a high anion gap metabolic acidosis. It is first important to distinguish DKA from hyperosmolar hyperglycemic state (HHS). These two diseases are distinguishable based on the level of hyperglycemia and the presence of ketoacidosis. In DKA, the serum glucose typically does not exceed 800 mg/dL, in contrast to HHS where the serum glucose usually exceeds 1,000 mg/dL. Furthermore, in HHS there is typically no ketone production and the osmolarity can approach 380 mOsm/kg.
(B) The preferred way to monitor treatment of DKA with IV fluids and insulin is to directly measure serum β-hydroxybutyrate. (C, D) However, given that this approach is not available in all hospitals, one can also monitor response to treatment with serum bicarbonate concentration (to analyze the improvement of metabolic acidosis) and also serum anion gap (to determine if the ketoacidosis is being corrected). Recall that serum anion gap estimates the unmeasured anions in the plasma; in DKA, this is useful information due to the presence of ketoacid anions. Urine ketones via nitroprusside test should not be used to monitor response because during treatment with insulin, β-hydroxybutyrate is converted to acetoacetate. Since nitroprusside measures acetoacetate and acetone (but not β-hydroxybutyrate), a positive nitroprusside test can give the false impression that the ketoacidosis has worsened. Furthermore, given that β-hydroxybutyrate is the predominant ketone in DKA, a serum nitroprusside test can be negative in the presence of moderate to severe ketosis.
A 39-year-old man presents with anxiety, sweating, and palpitations for the last 2 months. He has a blood pressure of 168/112 mmHg and his pulse is 84 beats per minute. The patient is diaphoretic on physical examination. Urine normetanephrine and metanephrine levels are found to be elevated.
Before surgical resection is performed for this condition, what medication must be administered?
Phenoxybenzamine. The patient in this question is presenting with pheochromocytoma, a catecholamine-secreting neuroendocrine tumor of the medulla of the adrenal glands. Eighty percent of pheochromocytomas are unilateral, 10% are bilateral, and 10% are extra-adrenal. Surgical resection of the pheochromocytoma is the treatment of choice, but the patient must be medically treated in preparation for surgery. Surgery can only proceed when the likelihood of intraoperative hypertension is reduced, so the medical treatment of choice is phenoxybenzamine, a nonspecific and irreversible α-blocker.
(A) Although giving a β-blocker in combination with an α-blocker has been recommended by some scholars for rate control, a pure β-blocker such as atenolol should never be given as single therapy with a pheochromocytoma due to the unopposed α-agonism that would result in severe hypertension. (C) Lisinopril is an ACE inhibitor often used in the treatment of hypertension (particularly diabetic patients for preventing the development of diabetic nephropathy), but not recommended as first-line medical treatment for pheochromocytoma. (D) Clonidine is a centrally acting α-2 agonist used in the treatment of hypertension. Although not used as a diagnostic modality in current practice anymore, a clonidine suppression test served to help make the diagnosis of pheochromocytoma.
A 31-year-old woman presents with difficulty breastfeeding. She recently birthed a healthy baby boy via normal vaginal delivery with what she describes as “moderately heavy blood loss.” The patient also has noted diffusely dry skin, cold intolerance, and weight gain. She has not initiated her menstrual cycle yet. Physical examination reveals diffuse xerosis and thinning hair.
Which of the following is the likely diagnosis?
Sheehan syndrome. The patient in this question is presenting with postpartum pituitary gland necrosis, also known as Sheehan syndrome. The cause of this disease is ischemic necrosis due to blood loss (sometimes hypovolemic shock) during and after childbirth. Sheehan syndrome can be explained first by the enlargement of the anterior pituitary gland (hypertrophy of lactotrophs) during pregnancy without an increase in vascular supply. Therefore, if childbirth is accompanied by hemorrhage or hypotension, the pituitary gland is vulnerable to necrosis. Of note, the posterior pituitary gland is not affected because it is directly supplied by arterial blood (as opposed to the anterior pituitary that is supplied venously). The most common symptom of Sheehan syndrome is absence of lactation (agalactorrhea) or difficulty lactating. Women can also present with hypothyroidism (but usually years after the episode) and adrenal insufficiency. Deficient gonadotropin release will cause amenorrhea and growth hormone deficiency is difficult to assess clinically but is associated with fatigue and somewhat decreased muscle mass.
(A) Autoimmune hypophysitis is associated with lymphocytic infiltration of anterior pituitary cells and usually takes well over 10 years for autoimmune symptoms to result. The symptoms are similar to Sheehan syndrome and include adrenal insufficiency, hypothyroidism, and hypogonadism; however, as opposed to agalactorrhea as seen in Sheehan syndrome, autoimmune hypophysitis can cause interruption of dopamine into the pituitary gland, which will cause an elevated prolactin level and cause milk production. (B) Hashimoto thyroiditis is an autoimmune disease of the thyroid gland, characterized pathologically by diffuse lymphocytic infiltration. Several antibodies are associated with Hashimoto thyroiditis, including thyroid peroxidase (TPO) antibodies and thyroglobulin antibodies. Given that this patient had not only presented with hypothyroid symptoms but also agalactorrhea, Hashimoto is unlikely. (C) Premature ovarian failure (POF) is an etiology of hypergonadotropic hypogonadism. The age of onset varies widely, but is defined as the loss of functional ovaries by the age of 40. It is associated with high levels of follicle-stimulating hormone (FSH) and decreased estrogen levels. Given this patient’s recent vaginal delivery in addition to her hypothyroid symptoms, POF is highly unlikely to be the diagnosis.
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