Week 38: Endo Pt. II

The management of diabetic ketoacidosis (DKA) involves administration of fluid, insulin, and potassium, in addition to searching for and treating any precipitant such as an infection. Initial hypokalemia is not common in DKA, and when present represents extreme total body potassium depletion. In this situation, potassium administration should be initiated before insulin. A reasonable guide is to delay insulin administration when the serum potassium level is below 3.3 mEq/L on presentation. Otherwise, as insulin and fluids are administered, hypokalemia worsens and predisposes patients to life-threatening respiratory paralysis and abnormal cardiac rhythms. Due to intracellular-to-extracellular shifting from acidosis and lack of insulin, most patients in DKA present with normal or slightly elevated serum potassium concentrations despite total body depletion of potassium. In the absence of renal failure, it is appropriate to initiate potassium administration in DKA when the potassium is 5.3 mEq/L or lower.

Sodium bicarbonate administration in DKA can delay a decrease in ketonemia and worsen hypokalemia. If administered, it is reserved for when the pH is less than 6.90 (not 7.15).

Insulin boluses are not required in the management of DKA and have not demonstrated benefit over beginning with an insulin infusion. If used, a bolus dose of 0.10 to 0.14 units/kg (not 0.01 units/kg) is appropriate.

During DKA treatment, administration of dextrose might be needed when the serum glucose falls but significant ketoacidosis remains. Guidelines recommend dextrose administration when the serum glucose is less than 200 mg/dL (not 350 mg/dL).

A. Magnesium sulfate IV
This patient is presenting with mild diabetic ketoacidosis likely secondary to acute infectious diarrhea from a contaminated food source. He is also hypokalemic, which is being repleted. Of the given answer choices, magnesium sulfate should be administered. Large volume diarrhea may cause total body potassium depletion, in addition to other electrolytes. Magnesium is an electrolyte that is often depleted in diarrhea as well, and repletion of hypomagnesemia is critical in the repletion of potassium, as hypokalemia often cannot be corrected until the magnesium deficit is reversed (PMID: 1728927).

B. Regular insulin IV
Potassium should be repleted first, until a repeat serum potassium level above 3.3 mEq/L (mmol/L) is documented, prior to administering insulin. Administering insulin in the setting of hypokalemia may worsen hypokalemia, risking the precipitation of cardiac arrhythmias.

C. Sodium bicarbonate IV
There is no indication for administering sodium bicarbonate in this patient.

D. Vancomycin IV
Although antibiotic administration may be indicated in this patient suffering from diabetic ketoacidosis likely secondary to acute infectious diarrhea (likely bacterial), vancomycin is a poor choice (primarily gram positive with little gram negative/anaerobic coverage).

Thyroid storm is a life-threatening condition often precipitated by a significant physiologic stressor such as childbirth, an infection, surgery (particularly on the thyroid in a patient with thyrotoxicosis), and trauma. In addition to specific treatment of thyroid hormone excess, it is imperative to search for and treat the precipitating stressor. Since infections are a common precipitant and might not be clinically obvious, the clinician should have a low threshold for starting broad-spectrum antibiotics. Specific treatment to address the thyroid hormone excess includes administration of these four agents: thionamide (propylthiouracil [PTU] or methimazole); iodine (an hour after the thionamide); corticosteroids; and beta-blockers.

Corticosteroids (dexamethasone or hydrocortisone) decrease conversion of T4 to the more active T3 and also decrease thyroid hormone release. They should be administrated routinely to patients in thyroid storm and not reserved just for those with coincident adrenal insufficiency.

The administration of a thionamide should precede that of iodine. Thionamides (propylthiouracil [PTU] or methimazole) inhibit thyroid peroxidase and decrease production of thyroid hormone. Iodine administration decreases the release and production of thyroid hormone by a feedback mechanism but must be given an hour or two following the thionamide to prevent the iodine from being used to produce even more thyroid hormone.

Plasmapheresis, a method of removing circulating thyroid hormone, can be considered for patients who are worsening despite maximal standard therapy and in those with contraindications to thionamide use. It is not a part of standard therapy and is not used routinely.

The neurologic deficits associated with most toxic and metabolic causes of significant altered levels of consciousness (including hypoglycemia) are typically symmetrical (nonfocal). However, a small but not insignificant number of patients with hypoglycemia presents with focal neurologic deficits, including hemiplegia. The rapid identification and correction of hypoglycemia in all patients, including those with focal neurologic deficits, is critical to avoid severe complications of a rapidly reversible condition and to avoid unnecessary imaging (brain imaging) and potential interventions (thrombolytic therapy).

Although adrenergic symptoms such as diaphoresis and tachycardia are common manifestations of hypoglycemia, bradycardia is less common, and none of these symptoms should be relied on to determine if a patient is hypoglycemic.

Release of the counterregulatory hormone epinephrine in the setting of hypoglycemia can result in a variety of adrenergic symptoms (anxiety, diaphoresis, palpitations, tachycardia, tremors). Hypotension is not expected and is not common.

Syncope is a transient loss of consciousness associated with a loss of postural tone that spontaneously reverses without medical intervention. When a patient becomes comatose from hypoglycemia, the body has exhausted its ability to counteract the hypoglycemia. Spontaneous reversal is very unlikely to occur. Syncope is not a common manifestation of hypoglycemia.

Destruction of the adrenal cortex in primary adrenal insufficiency (Addison disease) manifests with signs and symptoms of steroid deficiency (mineralocorticoids, glucocorticoids, gonadocorticoids) and increased adrenocorticotropic hormone (ACTH). The mineralocorticoid aldosterone stimulates the kidneys to reabsorb sodium and to excrete potassium. Aldosterone deficiency contributes to the presence of hyponatremia (seen 90% of the time), and hyperkalemia (seen 60% of the time). Deficiency in the glucocorticoid cortisol can lead to hypoglycemia, a common finding in children and infants. Signs and symptoms of gonadocorticoid deficiency are more common in women and include decreased axillary and pubic hair and decreased libido. Increased ACTH leads to skin hyperpigmentation. Causes of primary adrenal insufficiency include autoimmune disease (most common cause in Western countries), congenital conditions, drugs, hemorrhage, infections (tuberculosis is traditionally a common cause but is uncommon now in Western countries), infiltrative diseases (such as amyloidosis and sarcoidosis), and metastatic cancer.

Cortisol is involved with maintaining euglycemia. Cortisol deficiency in primary adrenal insufficiency leads to hypoglycemia, not hyperglycemia.

Hypercalcemia, not hypocalcemia, is seen in primary adrenal insufficiency. The hypercalcemia is thought to be a result of increased mobilization from bone and diminished renal excretion. It generally corrects quickly with hydration.

Aldosterone causes sodium resorption and potassium excretion. Aldosterone deficiency in primary adrenal insufficiency causes hyperkalemia, not hypokalemia.

A. Glucocorticoids prevents peripheral conversion of T3 to T4
Glucocorticoids blocks the peripheral conversion of T4 to T3.

B. Iodine blocks the release of T3, but not T4, from the thyroid gland
Iodine blocks release of T4, not T3, from the thyroid. T4 is converted to T3 peripherally.

C. Methimazole blocks peripheral conversion of T3 to T4
Methimazole works by inhibiting thyroid hormone synthesis.

D. Thionamides block de novo synthesis of thyroid hormones
Both T3 and T4 are released from the thyroid gland with the stimulation of TSH, but in the peripheral organs, T4 is converted to T3, which is the active form. Glucocorticoids blocks the peripheral conversion of T4 to T3. Iodine blocks the release of both T3 and T4 from the thyroid gland. Thionamides, such as PTU or methimazole, block de novo thyroid hormone synthesis. In addition, PTU (but not methimazole) also blocks T4 to T3 conversion.

A. ACTH serum level is increased
This is likely secondary adrenal insufficiency due to withdrawal of exogenous chronic steroid use, and is a result one would expect decreased ACTH levels

B. Aldosterone serum level is normal
This is likely secondary adrenal insufficiency due to withdrawal of exogenous chronic steroid use, and is a result of decreased ACTH levels with resulting low cortisol levels. Aldosterone levels are often unaffected in secondary adrenal insufficiency and will be normal in many cases, indicated by the lack of hyponatremia/hyperkalemia. Hypoglycemia, not hyperglycemia, is more commonly found in secondary adrenal insufficiency. Hyperpigmentation is found in primary, not secondary, adrenal insufficiency, due to increased prohormone production (the prohormone is cleaved into ACTH and melanocyte stimulating hormone).

C. Serum glucose is elevated
This is likely secondary adrenal insufficiency due to withdrawal of exogenous chronic steroid use. Glucose will likely be low

D. Hyperpigmentation of the skin is present
Hyperpigmentation is found in primary, not secondary, adrenal insufficiency, due to increased prohormone production (the prohormone is cleaved into ACTH and melanocyte stimulating hormone).

A. 11-beta-hydroxylase deficiency
11-beta-hydroxylase deficiency is a cause of congenital adrenal hyperplasia. However, 21 hydroxylase deficiency is the most common cause of CAH.

B. 21-hydroxylase deficiency
The correct answer is 21 hydroxylase deficiency. This patient’s presentation, particularly the hyponatremia and hyperkalemia, is consistent with congenital adrenal hyperplasia. 21 hydroxylase deficiency is the most common cause of CAH.

C. Carbamoyl phosphate synethetase I deficiency
Carbamoyl phosphate synethetase deficiency is a urea cycle disorder. It is a genetic deficiency that causes ammonia to build up in the blood.

D. Ornithine transcarbamylase deficiency
Ornithine transcarbamylase deficiency (OTC deficiency) is the most common urea cycle deficiency in humans. OTC deficiency results in high ammonia levels in the blood.

Metanephrine is an intermediate metabolite between epinephrine and vanillylmandelic acid. It is considered the most sensitive and specific test for identifying the presence of pheochromocytoma. Pheochromocytomas are catecholamine-producing adrenal tumors that can lead to hypertensive crises that may be lethal. The average age at diagnosis is approximately 40 years. The classic “rule of 10s” for pheochromocytomas is that approximately 10% are bilateral, 10% are extra-adrenal, and 10% are malignant. These tumors may arise sporadically or as a feature of an inherited condition such as multiple endocrine neoplasia, neurofibromatosis type 1 or von Hippel-Lindau disease. Typical clinical presentations include paroxysms of headaches, palpitations and profuse sweating: the classic triad of pheochromocytomas. Paroxysms usually last less than one hour and are brought about by exercise, position changes, surgery, urination or certain medications (e.g., metoclopramide, tricyclic antidepressants). Patients may present in a hypertensive crisis with acute pulmonary edema, intracranial hemorrhages, heart failure or dysrhythmias. Other clinical features may include anxiety or panic attacks, nausea, flushing, abdominal or back pain, pallor or generalized weakness. The first step in diagnosis is measuring biochemical metabolites called metanephrines, the methylated products of catecholamine catabolism. Diagnostic imaging for tumor localization is a secondary diagnostic method. Treatment includes total or partial adrenalectomy. Preoperative blood pressure management with oral alpha-adrenergic antagonists (e.g., phenoxybenzamine or prazosin) or beta-blockers (e.g., propranolol) can be used to keep blood pressure consistently less than 160/90 mm Hg.

5-HIAA (A), or 5-hydroxyindoleacetic acid, is a serotonin metabolite used in the diagnosis of carcinoid tumors. Serotonin (C) levels are not utilized for diagnosing neuroendocrine tumors, whereas serotonin metabolites (e.g., 5-HIAA) are. Vanillylmandelic acid (D) is the least specific catecholamine metabolite in testing for pheochromocytoma. It has greater utility in the initial diagnosis and surveillance testing for neuroblastomas.

Acquired hypoparathyroidism is most often the result of thyroid, parathyroid, or radical head and neck cancer surgery, or autoimmune damage of the parathyroid gland. This patient has symptoms consistent with hypocalcemia due to hypoparathyroidism. The parathyroid gland secretes parathyroid hormone which regulates calcium levels via effects on the bones, kidneys and gastrointestinal tract. Decreased levels of parathyroid hormone result in hypocalcemia and hyperphosphatemia. Classic symptoms consistent with hypocalcemia include neuromuscular irritability, such as perioral numbness, muscle cramping, paresthesias of the distal extremities, carpopedal spasm and seizures. Severe hypocalcemia can result in hypotension, dysrhythmias and cardiovascular collapse. A serum calcium level less than 8.5 mg/dL or an ionized calcium less than 2.0 mEq/L is considered diagnostic of hypocalcemia. Treatment depends on the current calcium level and presenting symptoms. Those with severe symptoms require intravenous calcium repletion with calcium gluconate. Patients with mild symptoms can be treated with oral calcium.

Laboratory findings of decreased calcium, decreased phosphorus, and increased parathyroid hormone (A) are consistent with hypocalcemia due to vitamin D deficiency. Hypoparathyroidism results in decreased calcium levels, not increased calcium levels (C). Increased calcium, decreased phosphorus, and increased parathyroid hormone (D) levels are consistent with primary hyperparathyroidism. Findings of hypercalcemia include lethargy, depression, constipation, ileus, kidney stones and abnormal bone remodeling.