Mkasap Endocrinology Notes

7/29/2019 Mkasap Endocrinology Notes

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MKASAP ENDOCRINOLOGY NOTES

Diabetes MellitusKey Points

Patients with impaired fasting glucose levels and impaired glucose tolerance are at increased risk fordeveloping type 2 diabetes mellitus. Women with a history of gestational diabetes mellitus are at very high risk (~50%) of developing type 2

diabetes within a decade.

Metformin is widely considered the best first-line antihyperglycemic agent for type 2 diabetes mellitus and may help prevent progression from prediabetes to diabetes; sulfonylureas are

typically used as second-line therapy.

In type 1 diabetes mellitus, an intensive insulin regimen involving at least three to fourdaily insulin injections or a continuous subcutaneous insulin infusion with a programmable insulin pump

is preferable.

Glycemic control needs to be maintained compulsively throughout gestation, with current glucose targets of 60 to 90 mg/dL (3.3 to 5.0 mmol/L) premeal and less than 120 mg/dL (6.7 mmol/L) 1

hour postmeal.

The mainstays of therapy for diabetic ketoacidosis are intravenous insulin and intravenous fluids. Microvascular complications in diabetes mellitus involve the kidneys (diabetic nephropathy), retinae

(diabetic retinopathy), and peripheral nerves (diabetic neuropathy); macrovascular complications

involve the coronary, carotid, and cerebral arteries (myocardial infarction); the aorta (stroke); and the

arterial supply to the lower extremities (gangrene).

Aggressive blood pressure control, particularly with angiotensin-converting enzyme inhibitors orangiotensin-II receptor blockers, slows the progression of diabetic nephropathy.

Clinical evaluation of the diabetic foot includes assessment of the vascular status of the leg and anevaluation of foot sensation with a standard 10-g monofilament.

Barring contraindications, all adult patients with diabetes mellitus who are older than 40years are nowadvised to take daily aspirin.

Disorders of the Pituitary GlandKey Points

Hypothalamic causes of pituitary dysfunction should be suspected when hypopituitarism isaccompanied by diabetes insipidus or hyperprolactinemia.

Hypopituitarism is commonly seen in patients after various brain injuries or insults, includingtraumatic brain injury, subarachnoid hemorrhage, neurosurgery, and cranial irradiation.

Lymphocytic hypophysitis, which usually occurs during or after pregnancy, causes hypopituitarism,possible symptoms of a mass lesion, and often adrenocorticotropic hormone insufficiency.

Adults with growth hormone deficiency have decreased muscle mass, increased fat mass, anddecreased bone mineral density; many also have decreased strength, endurance, and well-being.

A growth hormone stimulation test is necessary to diagnose growth hormone deficiency. In addition to prolactinomas, possible causes of hyperprolactinemia include medications, suprasellar

lesions, hypothyroidism, renal failure, hypothalamic disease, and pregnancy.


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Hyperprolactinemia also may be due to decreased clearance of prolactin because of chronic renalfailure and the presence of macroprolactin.

Dopamine agonists, in particular cabergoline, are the primary treatment for patients withprolactinomas.

Acromegaly carries a two- to threefold increased risk of mortality when levels of growth hormone andinsulin-like growth factor 1 are not normalized.

Long-acting preparations of the somatostatin analogues octreotide and lanreotide have been shown toreduce growth hormone and insulin-like growth factor 1 levels to normal in approximately 60% of

patients with acromegaly but result in only modest reductions in tumor size.

Incidentally found macroadenomas carry a 24% risk of enlargement over time and must be followedperiodically.

Somatostatin analogues are effective as adjunctive treatment of patients with thyroidstimulatinghormonesecreting adenomas.

Treatment of central diabetes insipidus includes desmopressin, which can be administered either orallyvia a metered nasal spray or subcutaneously by injection.

Cushing syndrome during pregnancy is associated with a substantially increased risk of prematurityand stillbirth.

Disorders of the Thyroid Gland

Key Points

The thyroid gland primarily secretes thyroxine with peripheral conversion to bioactivetriiodothyronine as required.

Adequate iodine intake is imperative for thyroid hormone production; pregnant and lactating womenrequire 50% or 100%, respectively, more iodine intake than the general population.

Both thyroid-stimulating hormone and free thyroxine levels should be measured to evaluate symptomsof thyroid disease.

The presence of antithyroid peroxidase and antithyroglobulin antibodies in euthyroid orsubclinically hypothyroid patients confers an increased risk of developing overt hypothyroidism.

Measurement of the thyroid-stimulating hormone receptor antibodies thyroid-stimulatingimmunoglobulin and thyrotropin-binding inhibitory immunoglobulin is best reserved for patients with

suspected euthyroid Graves ophthalmopathy, pregnancy complicated by Graves disease, or atypicalfluctuating hypo- or hyperthyroidism.

Thyrotoxicosis encompasses all forms of thyroid hormone excess, whereas hyperthyroidism relatesspecifically to excess hormone production by the thyroid gland.

Radioactive iodine uptake is elevated in hyperthyroidism and low in destructive thyroiditis andexogenous thyroid hormone exposure.

Color-flow Doppler ultrasonography is used to distinguish hyperthyroidism (high flow) fromthyroiditis (low flow).

The drug-free remission rate in patients with Graves disease who are treated with antithyroidal drugs isbetween 30% and 50% after 1 year of therapy.

Therapy with radioactive iodine (131I) should be avoided in patients with significant Gravesophthalmopathy.

Radioactive iodine (131I) or surgery can be definitive treatment of hyperthyroidism in patients withtoxic multinodular goiter and toxic adenoma.


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The classic course of destructive thyroiditis consists of a thyrotoxic release phase followed by ahypothyroid recovery stage, which in turn is followed by a return to euthyroidism.

Radioactive iodine uptake will be very low during the thyrotoxic phase of destructive thyroiditis butcan then rise to above-normal levels during the hypothyroid phase.

Amiodarone can induce two forms of thyrotoxicosis: iodine-induced hyperthyroidism (type 1) anddestructive thyroiditis (type 2).

The presence of antithyroid peroxidase antibodies suggests Hashimoto thyroiditis as the cause ofhypothyroidism.

Levothyroxine remains the mainstay of thyroid hormone replacement therapy in patients withhypothyroidism.

The suggested goal for serum thyroid-stimulating hormone levels in patients on levothyroxine therapyis 1.0 to 2.5 U/mL (1.0 to 2.5 mU/L).

Subclinical hypothyroidism may be associated with an increased risk of atherosclerosis and cardiacevents, but reversal of these effects with levothyroxine therapy has not been systematically studied.

Levothyroxine therapy is reasonable in patients with subclinical hypothyroidism who have increasedrisk factors for development of overt hypothyroidism.

Selection of thyroid nodules for fine-needle aspiration should be guided by nodule size and thepresence of worrisome ultrasound features (such as an irregular border, prominent central intranodularvascularity, microcalcifications, and hypoechogenicity).

The thyroid cancer risk is approximately the same for multinodular goiters and solitary nodules,whether found clinically or incidentally.

Nonthyroidal illness is commonly associated with changes in thyroid function tests; levothyroxinetherapy is not indicated.

The fetus is dependent on maternal thyroid hormone until its own thyroid becomes functional at 10 to12 weeks of gestation.

Maternal thyroxine demand increases substantially during pregnancy, and pregnant patients onlevothyroxine therapy may require a 35% to 50% increase in levothyroxine dosage during the first orsecond trimester.

Thyroid scans and radioactive iodine uptake testing are contraindicated in pregnant patients. Targeted therapy for thyroid storm should reduce thyroid hormone production/secretion by the thyroidgland, decrease peripheral conversion of T4 to bioactive T3, address associated adrenergic and

thermoregulatory changes, treat all precipitating factors, and aggressively reverse any systemicdecompensation.

Thyroid storm is associated with a mortality rate of 15% to 20%. Mental status changes and hypothermia are hallmark findings for myxedema coma. The primary pharmacologic therapy for myxedema coma is levothyroxine; use of liothyronine is more

controversial.

Underlying precipitants are common in myxedema coma and must be addressed along with thepatients thyroid abnormalities.

Disorders of the Adrenal Glands

Key Points

Central or secondary adrenal insufficiency results from loss of adrenocorticotropic hormone secretionfrom either chronic exogenous corticosteroid use or hypothalamic/pituitary diseases.


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The diagnosis of primary adrenal insufficiency is suspected when the serum cortisol level is low andthe adrenocorticotropic hormone level is high; the plasma aldosterone level is also low in primary

disease but not in central (or secondary) adrenal insufficiency.

Therapy for primary adrenal insufficiency includes corticosteroid therapy (hydrocortisone, prednisone,or dexamethasone), mineralocorticoid replacement (fludrocortisone), and (occasionally) adrenal

androgen therapy (in women); therapy for central or secondary adrenal insufficiency involves

corticosteroids alone at appropriate dosages.

Cushing syndrome occurs after prolonged exposure to endogenous or, more commonly, exogenouscorticosteroids; its diagnosis involves confirmation of persistent hypercortisolism associated with poorcortisol suppressibilty with dexamethasone.

Adrenocorticotropic hormoneindependent hypercortisolism is frequently due to a cortisol-producingadrenal tumor that is biochemically characterized by an elevated serum cortisol level associated with a

suppressed adrenocorticotropic hormone level.

The most appropriate treatment of Cushing syndrome is often surgery; for patients withadrenocorticotropic hormonesecreting pituitary adenomas, pituitary adenomectomy is appropriate

therapy.

Assessment of incidentally discovered adrenal masses should determine the nature of the mass (benignversus malignant) and its tissue of origin (primary versus metastatic).

Evaluation of an adrenal incidentaloma includes clinical assessment for signs of malignancy andadrenal function, assessment of the imaging characteristics of the mass (and of the other adrenal gland),and screening tests for possible increased hormone secretion.

All functioning tumors and those larger than 6 cm in diameter should be considered for surgicalremoval; nonfunctioning tumors smaller than 4 cm are often followed, and those measuring 4 to 6 cm

can be either surgically removal or clinically observed.

Pheochromocytoma can be diagnosed by measuring the plasma level and urinary excretion ofcatecholamines or their metabolites.

_-Blocker therapy should be avoided in patients suspected of having pheochromocytoma until theyreceive adequate _-adrenergic blocker therapy.

Treatment of pheochromocytoma involves laparoscopic adrenalectomy after appropriate preparationwith _-adrenergic blocking agents and reasonable control of blood pressure.

An aldosterone-to-renin ratio greater than 20 is highly suggestive of primary hyperaldosteronism. Confirmation of biochemically established hyperaldosteronism requires documentation of

nonsuppressibilty of elevated aldosterone secretion after high salt (oral or intravenous) intake.

Primary hyperaldosteronism caused by a solitary aldosterone-secreting adenoma is best treatedsurgically; bilateral adrenal hyperplasia is best managed medically with an aldosterone-receptorblocking agent.

The typical manifestations of adrenocortical carcinoma include clinical evidence of increased hormonesecretion (such as cortisol) or mechanical symptoms caused by a rapidly growing mass.

Surgical resection is the best therapeutic option for adrenocortical carcinomas and is best followed byuse of mitotane.

Reproductive Disorders

Key Points


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Borderline-low values for total serum testosterone should be further evaluated, particularly in elderlyand obese men.

Overt primary hypogonadism almost always causes infertility. Because hypogonadism may be the initial sign of a pituitary tumor or systemic disease, a thorough

workup is essential, especially in younger men.

Classic symptoms of androgen deficiency (and male hypogonadism) at any age include fatigue, loss of muscular strength, poor libido, hot flushes, and sexual dysfunction. A morning measurement of total serum testosterone level is the screening test of choice for male

hypogonadism.

Patients with moderately low (200-350 ng/dL [6.94-12.15 nmol/L]) total serum testosterone levelsshould have their free or bioavailable testosterone level determined.

Currently available testosterone replacement systems include injections, patches, gels, and buccalmucosa lozenges.

The cornerstone of the male infertility examination is analysis of semen, which should be obtainedafter 48 to 72 hours of sexual abstinence and analyzed immediately by qualified laboratory.

After pregnancy is excluded, polycystic ovary syndrome is the most common cause of secondaryamenorrhea.

A high follicle-stimulating hormone level indicates ovarian failure in a patient with amenorrhea. Withdrawal bleeding after progestin challenge indicates normal estrogen production and a nor outflowtract, whereas the absence of bleeding indicates a low estrogen level and/or an anatomic defect. The most common cause of hirsutism is polycystic ovary syndrome, which normally starts during

puberty, progresses slowly, and does not cause virilization or cushingoid features.

Measurement of the total serum testosterone level is recommended in patients with suspectedpolycystic ovary syndrome to exclude Cushing syndrome, androgen-producing tumors, and 21-hydroxylase deficiency.

Calcium and Bone Disorders

Key Points

Calcium and phosphorus balance is maintained within a narrow physiologic range through theinteractions of parathyroid hormone, vitamin D, and, to a lesser extent, calcitonin.

Measurement of serum levels of 25-hydroxy vitamin D3provides the best indicator of total bodyvitamin D stores.

Serum parathyroid hormone (PTH) levels are elevated or inappropriately normal in the PTH-mediatedcauses of hypercalcemia and are suppressed in the nonPTH-mediated causes.

Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient setting;cancer is the most common cause in hospitalized patients.

Minimally invasive parathyroidectomy with intraoperative measurement of the parathyroid hormonelevel is becoming the preferred surgical treatment of primary hyperparathyroidism.

Hyperparathyroidism associated with the multiple endocrine neoplasia syndromes typically involvesfour-gland hyperplasia, is associated with additional endocrine syndromes, and requires removal of threeor more glands for surgical cure.

The most common cause of acquired hypocalcemia is surgical excision of or vascular injury to theparathyroid glands during neck surgery.

Acute symptomatic hypocalcemia should be treated with intravenous calcium gluconate.


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In hypoparathyroidism, the serum calcium level should be maintained in the low-normal range toprevent hypercalciuria, renal stones, and renal failure.

Osteoporosis is present when the T-score is below2.5 on bone mineral densitometry. Oral alendronate, oral risedronate, and subcutaneous teriparatide reduce the risk of both vertebral and

nonvertebral fractures in patients with osteoporosis; annual intravenous administration of zoledronate

significantly reduces the risk of both vertebral and hip fractures in women.

Osteomalacia is characterized by decreased bone mineralization and low or normal ionized calcium,normal or high parathyroid hormone, and low vitamin D levels.

Paget disease should be treated if symptoms are present or if lytic involvement of the vertebrae, skull,weight-bearing bones, or areas adjacent to major joints occurs; bisphosphonates are the therapeutic

agents of choice for Paget disease

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Mkasap Endocrinology Notes