Hello, my name is Cindy Neunert. I’m a pediatric hematologist oncologist affiliated with NewYork-Presbyterian/Columbia and Morgan Stanley Children’s Hospital in New York.

Today, I am going to review the pathophysiology, incidence rate, clinical presentation, diagnosis, and treatment of immune thrombocytopenia.

ITP is an autoimmune syndrome involving antibody- and cell-mediated destruction of platelets and suppression of platelet production that may predispose patients to bleeding.^1-5

The incidence of ITP among adults in the United States is estimated to be 3.3 per 100,000 adults per year. The prevalence, or how many adults have ITP at any time, is about 9.5 cases per 100,000.⁶

ITP is classified by duration and includes newly diagnosed, defined as a 3-month duration from diagnosis; persistent, defined as a 3- to 12-month duration from diagnosis; and chronic, defined as a duration greater than 12 months from diagnosis.^7,8

The incidence of ITP in adults is bimodal, which peaks in young adults and the elderly.⁹ ITP in adults typically appears with no preceding viral or other illness and normally follows a chronic course.^8,9 The incidence in adults is approximately equal between the sexes, except between 30 to 60 years of age when the disease is more prevalent in women.⁸

Cases of ITP are categorized as primary, with no identified cause, or secondary, which can be attributed to an identified cause such as an underlying disease or drug exposure.^1,2

Next, let’s review the clinical presentation of ITP.

Signs and symptoms of ITP may include easy bruising, purpura, petechiae, hematoma, and mucocutaneous bleeding. Examples include nosebleeds and bleeding from the gums that is new or takes longer than usual to stop, blood in the urine or blood in the stool, bleeding from a cut that’s hard to stop, or menstrual bleeding that’s heavier than normal.^10-12

Bleeding episodes are mostly mucocutaneous.¹³

Intracranial hemorrhage and other major internal bleeding are rare but can be life threatening without early intervention.^2,10-12

Cutaneous signs of ITP may include easy bruising, oral petechiae, and petechiae of the skin, such as small, scattered spots that are red, pink, or purple.^10,11

There is currently no definitive laboratory test to diagnose ITP.⁶

ITP is typically diagnosed based on a complete blood count, or CBC, and additional urine and blood tests, such as a blood smear and antiplatelet antibody test.^10,11

A bone marrow aspiration may be done to examine the production of platelets and to rule out disorders that affect the bone marrow and reduce platelet production, such as acute leukemia or aplastic anemia.^6,11

A normal platelet count is generally between 150,000 to 450,000 platelets per microliter of blood.^11,14

According to an international working group of recognized expert clinicians, a diagnosis of immune thrombocytopenia requires a platelet count below 100,000 platelets per microliter of blood, with exclusion of other causes of thrombocytopenia.^2,7

Treatment of ITP is typically considered for patients with a platelet count below 30,000 platelets per microliter.¹⁵

The goal of therapy for ITP is to achieve a safe platelet count that prevents or stops major bleeding, rather than correcting the platelet count to normal levels.^7,15

The majority of patients with no or mild bleeding, defined as skin manifestations only such as petechiae and bruising, may not require treatment, just observation and regular monitoring of the platelet levels.^15,16

The 2 most common forms of first-line treatment used to stop bleeding and increase the platelet count to more than 30,000 platelets per microliter are corticosteroids and intravenous immunoglobulin, or IVIg. Steroids, if effective, increase platelet counts within several days to 2 to 3 weeks, whereas IVIg does the same, but is rapid, typically within 24 to 48 hours.^2,10,11,15

IVIg is usually reserved for patients with serious hemorrhage.^3,16

Second-line treatments include splenectomy, thrombopoietin, or thyroid peroxidase (TPO), receptor agonists, as well as more potent immunosuppressants.^15,16

Hello, my name is Gerald Appel. I’m a nephrologist at Columbia University Medical Center in New York.

I’m going to review the incidence rate, pathophysiology, clinical presentation, diagnosis, and treatment of anti-glomerular basement membrane, or anti-GBM, disease and membranous nephropathy, also called membranous glomerulonephritis.

Now let’s take a look at the first type of glomerular nephropathy: anti-GBM disease. The incidence of anti-GBM disease in the general population approaches 0.5 to 1.0 case per million each year. Although all age groups are affected, there is a bimodal age distribution with males predominating in the younger age group and females in the older group. Overall, there is a slight male preponderance.^1,2

Both genetic and environmental factors appear to be important in the etiology of anti-GBM disease.²

Like many other autoimmune diseases, anti-GBM disease shows strong genetic linkage with human leukocyte antigen, or HLA, alleles. Infectious agents, smoking, and exposure to hydrocarbons have been causally associated with disease onset.¹

Anti-glomerular basement membrane disease is rare in the general population, but it is a well-characterized autoimmune disorder with autoantibodies directed at specific component antigenic targets within the glomerular and pulmonary basement membrane.^1-4

Signs and symptoms of anti-GBM disease may include elevated serum creatinine levels, swelling of feet or legs, hematuria, proteinuria, and in those with pulmonary involvement, shortness of breath, cough, and hemoptysis.^2,5-7

Patients may also report dark-colored urine and oliguria.^2,3

Several test results may be used to suggest a diagnosis of anti-GBM disease, including a urinalysis, blood analysis, complete blood cell count, or CBC, and a chest X-ray, particularly if pulmonary disease is present.⁷

The presence of serum anti-GBM antibodies is extremely suggestive of this diagnosis.⁷

A definitive diagnosis of anti-GBM disease is confirmed with either kidney or pulmonary tissue showing the presence of linear antibody staining along the glomerular or pulmonary basement membranes. Lung tissue is typically not sought due to the invasiveness of the procedure and the more technically difficult immunofluorescence process.^7-9

If anti-GBM disease is suspected, urgent evaluation and treatment is needed,^3,9 including potentially referring patients to a specialist for additional diagnostic tests and/or treatments. Renal outcome depends on the degree of renal damage at initiation of effective treatment.²

Without early intervention and treatment, the outcome can be very poor, because anti-GBM disease can lead to renal failure requiring dialysis or transplantation and can be life threatening if left untreated.^2,3

Once diagnosis is confirmed, there are 2 steps involved in the treatment. The first step is to remove the circulating anti-GBM antibody from the blood by plasmapheresis. The second step is to prevent further autoimmune antibody production through immunosuppression. Most patients are given large-dose intravenous (IV) corticosteroids, followed by daily oral steroid therapy. An oral or IV immunosuppressant is used in conjunction with steroid therapy to reduce new antibody production.^2,4

Now, let’s take a look at membranous nephropathy, or MN.

Membranous nephropathy is the leading cause of nephrotic syndrome in Caucasian adults,10 with symptoms including proteinuria, low blood protein level, high cholesterol levels, and swelling.¹¹

Membranous nephropathy affects more men than women, and it is seen more often in patients older than 40 years of age.^11,12

In approximately two-thirds of membranous nephropathy cases, the etiology is idiopathic.10 Up to 70% of such patients will have circulating antibodies to the phospholipase A2 receptor. In the remaining one-third of patients, who rarely if ever have circulating antibodies to this receptor, membranous nephropathy is considered secondary.¹³ It may be associated with or caused by other conditions—such as systemic lupus erythematosus, lung and colon cancer, and hepatitis B and C infection—or induced by certain medications.^10,11,14-16

Membranous nephropathy is caused by the thickening of a part of the glomerular basement membrane, resulting in increased permeability of the glomerular capillary walls and leakage of large amounts of protein into the urinary filtrate. If this persists over a long period of time, the glomerular capillary walls become thickened and eventually the glomeruli scar, leading to renal failure.^11,12,17,18

Signs and symptoms of membranous nephropathy often begin slowly and progress over time. The most noticeable symptom is edema, which typically starts in the feet and legs and may move into the hips and abdomen. Other symptoms may include swelling around the eyes, weight gain, foamy urine caused by proteinuria, excessive urination at night, high cholesterol, high blood pressure, and fatigue due to low levels of protein in the blood.^{11,12,16,19,20}

Several test results can suggest a diagnosis of membranous nephropathy. Urinalysis findings may demonstrate proteinuria and microscopic hematuria.^10,11

The glomerular filtration rate, or GFR, which is the speed at which the kidneys cleanse the blood, is often normal or decreased.^10,11,21

Blood analysis may demonstrate elevated serum creatinine, decreased serum albumin, and the presence of anti-phospholipase A2 receptor antibodies.^22-24

A kidney biopsy is used to confirm the diagnosis of membranous nephropathy.¹¹

Light microscopy will show thickened glomerular basement membrane.¹²

Electron microscopy will show subepithelial electron-dense deposits and basement membrane spikes separating the deposits.¹⁰

If membranous nephropathy is suspected, prompt evaluation and treatment is advisable,10,25 including potentially referring patients to a kidney specialist for additional diagnostic tests, treatments, or both.

The goals of treatment are to reduce the symptoms and slow the progression of the disease.¹¹

Early detection and treatment of nephropathies may decrease the risk of poor outcomes.²⁵

Therapy directed to improve the nephrotic state includes ACE inhibitors, A2 receptor blockers, or both to help control blood pressure and reduce intraglomerular pressures and proteinuria, which is the most important way to delay kidney damage.^10,11

Patients should also be instructed to follow a low-salt diet because a high intake can significantly impair the beneficial effects of the ACE inhibitors and A2 receptor blockers.¹⁰

Diuretics may also be prescribed to help with edema.¹¹

In patients with medium to high risk of membranous nephropathy progression, immunosuppressive agents may be used.^10,24

In terms of outcomes seen in the general population, some patients may have persistent, fluctuating degrees of proteinuria but stable renal function; others may undergo spontaneous remission; and still others may develop progressive renal impairment, eventually leading to end-stage renal disease or failure.^25,26

Hello, my name is Jennifer Perkins, an endocrinologist at Duke University Hospital in Durham, North Carolina.

I am going to review the pathophysiology, incidence, clinical presentation, diagnosis, and treatment of hyperthyroidism and hypothyroidism.

First, let’s take a look at hyperthyroidism.

Hyperthyroidism is a condition caused by the thyroid gland either making or releasing too much preformed thyroid hormone, which can enlarge the thyroid gland and accelerate the body’s metabolism.¹

Hyperthyroidism occurs in about 1% of people, or 1 person out of 100, in the United States.2 Graves’ disease accounts for 60% to 80% of these cases.³

Hyperthyroidism can present with multiple symptoms that vary according to the age of the patient, duration of illness, magnitude of hormone excess, and presence of comorbid conditions.³

Some of the most common signs and symptoms of an overactive thyroid in hyperthyroidism may include racing heart, tremor, palpitations, weight loss, diarrhea, heat intolerance, and amenorrhea.^1,6,9

Hyperthyroidism is typically diagnosed by measuring the level of thyroid-stimulating hormone, or TSH, in the blood.¹

Although reference ranges are not necessarily standardized nor agreed upon and are assay dependent, according to the American Thyroid Association guidelines, patients with TSH levels below 0.1 milli-international units of hormone per liter of blood should be diagnosed with and treated for hyperthyroidism. Patients with comorbidities such as heart disease and osteoporosis should be treated when their TSH levels are below <0.35 milli-international units of hormone per liter of blood.⁷

The goals of therapy are to help correct the hypermetabolic state with the fewest side effects and the lowest risk of hypothyroidism possible.¹

Treatment options will depend on several factors, including patient age, physical condition, the underlying cause and severity of the hyperthyroidism, and patient preferences.³

There are several common mainstay options for treating persistent hyperthyroidism and Graves’ disease, including oral antithyroid drugs, oral radioactive iodine, and surgery.^1,3,8

Beta blockers, iodides, and corticosteroids can be used together with the primary treatment as adjunctive therapy to increase effectiveness.^3,7,8

Beta blockers help to relieve the adrenergic symptoms of hyperthyroidism, such as tremors, palpitations, and heat intolerance.^3,8

Iodides are used for rapid reduction of thyroid hormone levels, typically only used as a bridge to surgery. They may also be used in those who do not tolerate antithyroid drugs and in those with severe cardiac disease.^3,7,8 However, if iodides are used for more than 2 to 3 weeks, a recurrence of hyperthyroidism may occur.^7,11

Now, let’s take a look at hypothyroidism.

In contrast, hypothyroidism is a condition where the thyroid gland does not secrete the necessary amount of hormones.¹² The thyroid gland can be larger earlier in the disease when inflamed and then may shrink and become fibrotic over time.^13,14

Hypothyroidism occurs in about 5% of people, or 5 people out of 100, in the United States.¹⁵

Chronic autoimmune thyroiditis, also called Hashimoto’s thyroiditis, is the most common cause of hypothyroidism.¹⁴

Hypothyroidism can present with a myriad of clinical signs and symptoms that vary according to the severity of the hormone deficiency, age, and sex. The most common symptoms of hypothyroidism are fatigue and cold intolerance.¹⁶

Other common symptoms include weight gain, constipation, depression, and forgetfulness.^4,12,16

The best method for diagnosing hypothyroidism is the TSH blood test, followed by a thyroid hormone test, if needed.¹²

Patients with TSH levels above 10 milli-international units of hormone per liter of blood should be treated for primary hypothyroidism.^12,19

Symptomatic patients with TSH levels of 4.5 to 10 milli-international units of hormone per liter of blood may benefit from treatment, too.¹⁹

Women with thyroid disease or positive antibodies with TSH levels above 2.5 milli-international units of hormone per liter of blood should seek care prior to conception.²⁰

Standard of care for patients who are overtly hypothyroid, with little residual thyroid function, includes taking an oral synthetic thyroid hormone.^12,19

The dosage will depend on the patient’s age, sex, and body size. Those without a thyroid gland may need higher doses, while those patients with milder thyroid hormone deficiencies may require lower doses.

Dose adjustments are guided by serum TSH determinations following initiation of therapy.¹⁹

Periodic TSH tests are also crucial for determining the optimal starting dosage of medication and for making any necessary adjustments over time.¹²