TO TABLE OF CONTENTS
Endocrine Causes of Chronic Fatigue: A
Review of Symptoms, Treatments
By Theodore C. Friedman, MD, PhD and
Diagnosing chronic fatigue and immune dysfunction syndrome
(CFIDS) can be a
time-consuming and complex process. Numerous diseases and disorders cause
long-term fatigue — and doctors must eliminate all of them before arriving at a
diagnosis of CFIDS.
Diseases of the endocrine system are among the most common
causes of non-CFIDS fatigue, and in some cases
can closely mimic CFIDS. The endocrine system
includes a number of glands that produce hormones controlling metabolism,
growth, sexual development and other body processes. In this article, Dr.
Theodore Friedman discusses several key endocrine causes of fatigue — and ways
to differentiate them from CFIDS and treat
Although fatigue may be the earliest manifestation of
endocrine diseases, patients usually will have other symptoms as well. These
endocrine symptoms differ from the classic infectious symptoms associated with
CFIDS such as fever, sore throat and swollen
joints. Symptoms suggestive of an endocrine cause of fatigue as opposed to an
infectious cause or immunological cause are listed in Table 1. If the patient
has some of the symptoms listed in the table, an endocrine cause of chronic
fatigue may be suspected.
Some of the more common endocrine diseases that often cause
chronic fatigue include the following:
Impaired conversion of the thyroid
hormone T4 to T3
Adult growth hormone deficiency
A quick reference guide to several major endocrine causes of
fatigue is provided below. Because these diseases can be tricky to diagnose, a
primary care physician should carefully consider a specialist who is current on
the latest developments in endocrinology and is experienced in its many
subtleties. These endocrine diseases, unlike
CFIDS, are often very treatable.
This condition, marked by a
reduced production of thyroid hormone, is probably the most common endocrine
cause of chronic fatigue. Besides fatigue, patients may also have weight gain,
sluggishness, decreased memory, coarse, dry skin, heavy periods and fluid
accumulation, and also may feel cold. They could have an enlarged thyroid
There is growing realization that patients with mild (often
called subclinical) hypothyroidism may show only mildly elevated thyroid
stimulating hormone (TSH, a marker for the condition) and the symptom of
fatigue. Patients with a goiter found by an experienced endocrinologist, or with
positive anti-TPO antibodies, are more likely to benefit from thyroid hormone
It is also noteworthy that patients with pituitary causes of
hypothyroidism may have low-but-normal levels of TSH and the thyroid hormone T4.
Some endocrinolgists are finding that treatment with levothyroxine (synthetic
T4) alone is not enough in patients with hypothyroidism and that some patients
need treatment with liothyronine (synthetic T3) in addition to T4.
Cushing’s syndrome is often
due to a tumor of the pituitary gland. This tumor will cause the adrenal glands
to make too much of the stress-related hormone cortisol. Fatigue may be the
earliest presentation of Cushing’s syndrome. Weight gain, trouble sleeping,
irregular periods, extra hair growth (hirsuitism) and depression are other
common symptoms. Many doctors, who have only seen textbook, severe cases of
Cushing’s syndrome, may not recognize milder cases.
Cushing’s syndrome may be very difficult to diagnose. Early in
the disease progression, some of the screening tests may be normal. Patients
should be sent to an endocrinologist who may collect urine for cortisol (urinary
free cortisol (UFC) and 17-hydroxysteroids) or collect nighttime salivary
cortisol samples. Surgery to remove the tumor is often the treatment for
The metabolic syndrome
The metabolic syndrome
(also called Syndrome X or insulin resistance) is a newly identified syndrome
associated with fatigue. These patients have elevated insulin levels and central
(abdominal) obesity. They often have high blood pressure and hyperlipidemia
(high cholesterol and triglycerides). Men may have gout or balding, and women
may have extra hair growth and irregular periods. A high carbohydrate diet may
be involved in this disease. These patients are at risk for having heart
disease. In addition to weight loss and exercise, these patients may also
benefit from a low carbohydrate diet or treatment with agents that improve
insulin action, such as metformin (Glucophage).
Your endocrinologist may want to measure fasting insulin and
glucose levels to make the diagnosis. A simple blood glucose level or even a
glucose tolerance test may not be sufficient to detect insulin resistance.
Growth hormone deficiency
Adults with growth
hormone deficiency have severe fatigue, weight gain (especially around the
abdomen), are often depressed and have poor quality of life. Children, but not
adults, with growth hormone deficiency are short. Most cases of adult growth
hormone deficiency are due to damage to the pituitary gland, often due to a
tumor (usually not malignant).
Symptoms of growth hormone deficiency may be the first
manifestation of a pituitary tumor. However, a tumor is not always present even
though a patient is truly growth hormone deficient.
Growth hormone therapy is effective only for patients who are
truly GH deficient. Patients with other causes of chronic fatigue will not be
helped by growth hormone therapy and some may be harmed by it. It is very
important to be correctly diagnosed. You should not take growth hormone unless
you are found to be growth hormone deficient.
Growth hormone is secreted in pulses so a single measurement
of blood levels is not helpful. Rather than measuring a random growth hormone,
your endocrinologist will probably screen you by measuring a plasma IGF-1 level.
If it is low, your doctor may do sophisticated tests that stimulate growth
hormone secretion and measure its levels. These tests should only be performed
by personnel experienced with GH testing.
Many female patients develop
fatigue around the time of menopause. This could be due the drop in estrogen at
that time, although decreases in testosterone may also play a role.
Hormone replacement therapy has been a common treatment for
this condition. Recently, however, many women have been told by their doctors
not to take estrogen due to two recent studies that showed a slight increase in
risk of breast cancer and heart disease in patients taking a synthetic estrogen,
called Premarin, and a synthetic progestin, called Provera.
But there have not been any studies showing increased risk in
breast cancer and heart disease in women taking just estrogen or more natural
forms of estrogen plus progesterone. In fact, many women note an improvement in
their fatigue when their low levels of estrogens are increased by being placed
on estrogen supplementation.
Estrogen replacement is a complex subject as estrogens can
interact with many other hormonal systems. Even the form of the estrogen is
important. Oral estrogen can alter thyroid requirements and actions of growth
hormone. Yet estrogen delivered by patch or by a gel does not interfere in the
same way. The effects of different preparations of estrogen even vary from
patient to patient. The body itself makes different estrogens, including
estradiol and estriol.
The symptom of fatigue may be relieved with more specific
estrogen preparations. Relying solely on the common but rather generic Premarin,
which is a broad preparation from the urine of pregnant horses, may not be the
best course for many women.
Low levels of
testosterone may be due to a pituitary, adrenal or ovary/testis problem. If
either men or women have fatigue and low libido (interest in sex), their doctor
may want to measure their testosterone levels. If low levels are found,
measurement of the pituitary hormones, LH and FSH, may help find the source of
the problem. There are many good products for testosterone replacement in men,
including gels and patches.
There are fewer options for testosterone replacement in women,
although taking DHEA, which gets converted to testosterone, may be one option.
(Editor’s note: Dr. Friedman is currently performing a study of testosterone
replacement in women with pituitary problems. For more information see his Web
(Addison’s disease), like Hashimoto’s thyroiditis, is an autoimmune disease.
Patients with one autoimmune disease often develop another. Patients with
adrenal insufficiency can have severe fatigue, weight loss, abdominal pain and
diarrhea, increased skin pigmentation and salt craving. They often have low
blood pressure when they stand (orthostatic hypotension).
The adrenal gland makes two important hormones, cortisol and
aldosterone. Cortisol, the glucocorticoid hormone, is the hormone involved in
the stress system, while aldosterone, the mineralocorticoid hormone, regulates
salt and water retention. It has recently been found that some patients with
Addison’s disease may have deficiencies of only cortisol, only aldosterone, or
both and that deficiencies of either hormone may give patients the symptoms of
fatigue. Aldosterone deficiency may lead to lightheadedness, dizziness on
standing, salt-craving and palpitations. Cortisol deficiency may lead to
abdominal pain, diarrhea, weight loss or fever.
Your endocrinologist may want to measure hormones such as
cortisol, ACTH, DHEAS, renin and aldosterone. You may be treated with
replacement hormones including hydrocortisone, fludrocortisone (Florinef) and
Finding out more
More information about the
endocrine causes of fatigue can be found at
http://www.goodhormonehealth.com. The Web site includes an easily
readable table of symptoms associated with excesses and deficiencies of various
hormones. It is hoped that a treatable endocrine cause for debilitating fatigue
can be found for some patients.
Dr. Friedman is an associate professor in the Division of
Endocrinology at the
of Medicine &
of Medicine in Los Angeles. He can
be reached at (310) 335-0327, or by e-mail at
Symptoms suggestive of an endocrine
cause of fatigue
Irregular periods in women
Dizziness on standing
Weight gain in spite of dieting
Body hair growth in women
Loss of memory
Decreased interest in sex
Trouble with erections in