Cushing Syndrome

Background

Cushing syndrome is caused by prolonged exposure to elevated levels of either endogenous glucocorticoids or exogenous glucocorticoids
Individuals often complain of proximal muscle weakness, easy bruising, weight gain, hirsutism, and, in children, growth retardation. Hypertension, osteopenia, diabetes mellitus, and impaired immune function may occur.

Pathophysiology

Excess levels of either exogenously administrated glucocorticoids or endogenous overproduction of cortisol causes Cushing syndrome. Endogenous glucocorticoid overproduction or hypercortisolism that is independent of adrenocorticotropic hormone (ACTH) is usually due to a primary adrenocortical neoplasm (usually an adenoma but rarely a carcinoma). Bilateral micronodular hyperplasia and macronodular hyperplasia are rare causes of Cushing syndrome
ACTH-secreting neoplasms cause ACTH-dependent Cushing syndrome. They usually are due to an anterior pituitary tumor, that is, classic Cushing disease (80%).
Non-pituitary ectopic sources of ACTH, such as an small-cell lung carcinoma, or carcinoid tumor,
Ectopic corticotropin-releasing hormone (CRH) secretion leading to increased ACTH secretion comprise a very rare group of cases of Cushing syndrome
Most cases of Cushing syndrome are due to exogenous glucocorticoids.

The annual incidence of endogenous Cushing syndrome has been estimated at 13 cases per million individuals. Of these cases, approximately 70% are due to Cushing disease, that is, a pituitary ACTH-producing tumor; 15% to ectopic ACTH; and 15% to a primary adrenal tumor.

Two catastrophic medical crises that occur in glucocorticoid excess states are perforated viscera and opportunistic fungal infections
Exposure to excess glucocorticoids results in multiple medical problems, including hypertension, obesity, osteoporosis, fractures, impaired immune function, impaired wound healing, glucose intolerance, and psychosis

Exogenous steroids suppress the HPA axis, with full recovery taking as long as a year after cessation of glucocorticoid administration. Thus, patients who are on or who have taken steroids are at risk for developing an adrenal crisis if steroids are stopped or not increased during an acute illness.

For that … If cortisone medication to discontinue

then… tapering down !!!

Similarly, lack of cortisol leading to an adrenal crisis may occur in patients with endogenous Cushing syndrome who have undergone resection of an ACTH-producing or cortisol-producing tumor or who are taking adrenal steroid inhibitors.

History…

Patients with Cushing syndrome may complain of weight gain, especially in the face, supraclavicular region, upper back, and torso.

Frequently, patients notice changes in their skin, including purple stretch marks, easy bruising, and other signs of skin thinning.

Because of progressive proximal muscle weakness, patients may have difficulty climbing stairs, getting out of a low chair, and raising their arms.

Menstrual irregularities, amenorrhea, infertility, and decreased libido may occur in women due to inhibition of pulsatile secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which likely is due to interruption of luteinizing hormone-releasing hormone (LHRH) pulse generation.
 
In men, inhibition of LHRH and FSH/LH function may lead to decreased libido and impotence.

Psychological problems such as depression, cognitive dysfunction, and emotional lability may develop

New-onset or worsening of hypertension and diabetes mellitus, difficulty with wound healing, increased infections, osteopenia, and osteoporotic fractures may occur.

Patients with an ACTH-producing pituitary tumor (Cushing disease) may develop headaches, polyuria and nocturia, visual problems, or galactorrhea

If sufficient mass effect from the tumor is present on the anterior pituitary, hyposomatotropism, hypothyroidism, hyperprolactinemia or hypoprolactinemia, and hypogonadism may develop.

Complications:
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Osteoporosis
Increased susceptibility to infections
Hirsutism
Diabetes mellitus
Hypertension
Risk for adrenal crisis
Panhypopituitarism
Diabetes insipidus

Hyperthyroidism (Treatment)

1) β-blockers (symptom control)
Propranolol (Inderal ®)
Atenolol (Tenormin ®)
Metoprolol (Lopressor ®)

2) 131-RAIA (70% thyroidologists prefer)
Dosing
Graves: 10-15 mCi
Toxic MNG/Adenoma: 20-30 mCi
Absolute contraindications
Pregnancy and lactation (excreted in breast milk)!
Pregnancy should be deferred for at least 6 months following therapy with radio-active 131
It is advisable to avoid 131-Rdio-active iodine therapy in patients with active moderate severe Graves’ ophthalmopathy.
3) Antithyroid Drugs (30% thyroidologists prefer)
Propylthiouracil (PTU)
100 mg bid-tid to start
Methimazole
10X more potent the PTU
10 mg bid-tid to start
Complications of ATD’s
Agranulocytosis (1/200-500)
usually presents w/ acute pharyngitis/ tonsilitis or pneumonia.
Rash
Hepatic necrosis, Cholestatic jaundice
Arthralgia
4) Surgery (sub-total thyroidectomy)
Indications
Patient preference
Large or symptomatic goiters
When there is question of malignancy
Need to be euthyroid prior to surgery
To ↓ the risk of arrhythmias during induction of anesthesia
To ↓ the risk of thyroid storm post operatively
ATD’s + β-blockers
Risks
Permanent hypoparathyroidism
Recurrent laryngeal nerve problems
Permanent hypothyroidism

Breast Cancer Treatments

TREATMENT OPTIONS:Treatment choices for the person with cancer depend on the stage of the tumor, that is, if it has spread and how far.
Treatment options may include surgery, radiation, chemotherapy, hormone therapy, and immunotherapy:
Surgery is the oldest form of treatment for cancer. Surgery offers the greatest chance for cure for many types of cancer.
Radiation therapy uses high-energy particles or waves, such as x-rays or gamma rays, to destroy or damage cancer cells and may be recommended for the treatment of some types of breast cancer.
Chemotherapy is the use of medicines (drugs) to treat cancer. Systemic chemotherapy uses anticancer drugs that are usually given into a vein or by mouth. These drugs enter the bloodstream and reach all areas of the body, making this treatment potentially useful for cancer that has spread and may be recommended for the treatment of some types of breast cancer.
Hormone Therapy is treatment with hormones, drugs that interfere with hormone production or hormone action, or surgical removal of hormone-producing glands to kill cancer cells or slow their growth . may be recommended for the treatment of some types of breast cancer.

Decision about treatment should be made with HCP.

A Good Breast Health Plan

Mammography refers to x-ray of the breast. Mammography is used to detect and diagnose breast disease both in women who have breast symptoms (problems such as a lump, pain or nipple discharge) and women who are asymptomatic (no breast complaints).
Early diagnosis is the key to surviving breast cancer. Mammography can prevent thousands of breast cancer deaths each year. Regular screening mammograms are the best way to detect breast cancer early, when it is easiest to treat.
When having a mammogram, women should ask their doctor when they can expect to receive the results. Regulations facilities to send women their results within 30 days.
Older women are at highest risk for breast cancer, yet they are the least likely to get mammograms.
The ACS can tell women where they can get a mammogram. Call 1-800-ACS-2345.
By law, all mammography facilities must be certified by the U.S. Food and Drug Administration.
They must meet standards for the equipment used, people who work there, and records that are kept.
Mammography can detect cancers several years before it can felt through a clinical exam.
Breast abnormalities are discovered in one of three ways: by a woman herself, by her HCP during a physical exam, or by a mammogram. Many breast cancers are found by the woman herself, but the smallest cancers are found by mammograms.
Low-cost and free mammograms are available to low-income women through their local or state health department.
Annual mammograms are covered by Medicare and Medicaid.
Most breast lumps are not cancer.
Clinical Breast Examination
A clinical breast examination (CBE) is an examination of your breasts by a health professional, such as a physician, nurse practitioner, nurse, or physician assistant.
For this examination, you undress from the waist up. The health professional will first inspect (look at) your breast for changes in size or shape.
Then, using the pads of the fingers, the examiner will gently palpate (feel) your breasts. Special attention will be given to the shape and texture of the breasts, location of any lumps, and whether such lumps are attached to the skin or to deeper tissues.
The area under both arms and above and below the collar bones will also be examined.
During the CBE is a good time for the health professional to teach breast self-examination to the woman who does not already know how to examine her breasts.
Ask your doctor or nurse to teach you and watch your technique.
Breast Self-Examination (BSE)-
Performing monthly breast self-examinations, beginning at age 20
During the CBE is a good time for the health professional to teach breast self-examination to the woman who does not already know how to examine her breasts.
Ask your doctor or nurse to teach you and watch your technique.

Breast Cancer Risk Factors

Obesity: Being overweight increases the risk, especially after reaching menopause if that weight gain took place during adulthood.
Exercise: Exercise can lower breast cancer risk by about 60% in adults. More research is being done to confirm these findings.
Breastfeeding: Studies have shown that breastfeeding lowers breast cancer risk, especially is breastfeeding lasts 1½ to 2 years. One study found that having several children and breastfeeding could reduce the risk of breast cancer by half. This may be because breastfeeding lowers a woman’s total number of menstrual periods.
Alcohol: Alcohol is clearly linked with an increased risk of breast cancer. Those who have 2 to 5 drinks daily have about 1½ times the risk of women who drink no alcohol.
HRT: It has become clear that long term use (several years) of combined HRT (estrogens together with progesterone) for the relief of menopause symptoms may slightly increase the risk of breast cancer as well as the risk of heart disease, blood clots, and strokes. The breast cancers are also found at a more advanced stage. As well, HRT seems to reduce the effectiveness of mammograms.
Birth control pills: studies have found that women now using birth control pills have a slightly increases risk of getting breast cancer.
Not having children before the age of 30 increases a woman’s risk by 40%.

What Is Breast Cancer ?

What Is Breast Cancer?
Most kinds of cancer are named after the part of the body where the cancer first starts.
Breast cancer begins in the breast tissue.
Inside the breasts are glands that produce and release milk after a woman has a baby.
The glands that make the milk are called lobules and the tubes that connect them to the nipple are called ducts.
The breast itself is made up of lobules, ducts, and fatty, connective, and lymphatic tissue.
Lymph is a clear fluid that contains immune system cells and tissue waste products.
The fluid is carried in lymph vessels that lead to small, pea-sized collections of tissue called lymph nodes.
Most lymphatic vessels of the breast lead to lymph nodes under the arm. They are called axillary's nodes.

What Is Cancer ?

Cancer: cancer is not just one disease but rather a group of diseases.
All forms of cancer cause cells in the body to change and grow out of control.
Most types of cancer cells form a lump or mass called a tumor.
The tumor can invade and destroy healthy tissue. Cells from the tumor can break away and travel to other parts of the body. There they can continue to grow.
This spreading process is called metastasis. When cancer spreads, it is still named after the part of the body where it started.
For example, if breast cancer spreads to the lungs, it is still breast cancer, not lung cancer.