HIV/Endocrine Update

HIV infection apparently fosters problems of the endocrine
system that may be both common and commonly overlooked. At least
some of these are treatable in symptomatic people, and so lately
have been attracting attention.

The endocrine system comprises a network of glands that
secrete hormones -- complex messengers which evolved to instruct
the body on an enormous number of activities, including daily
metabolism, sexuality and reproduction, and responses to stress.
Because HIV disease can dampen an effective endocrine response to
illness, hormones may fill a therapeutic role to facilitate
recovery or stop a progressive debilitation.

Last December, an article in AIDS TREATMENT NEWS #140
discussed the association between HIV progression and
deficiencies of the hormones dehydroepiandrosterone (DHEA) and
hydrocortisone (cortisol). In the meantime, several people have
shared with us information or experience that helps expand that
discussion.

In our first report, we said that physicians generally do
not advocate hormone treatments except as replacement therapy
when a particular gland is diseased, such as in CMV infection of
the thyroid. However, that assertion paints an incomplete
picture, for a couple of reasons.

For one, hormones administered as drugs are not uncommon
treatments for a variety of disease effects which are not related
per se to endocrine problems. For example, dexamethasone
(Decadron) is one part of a frequently used cancer chemotherapy
combination; megestrol acetate (Megace) is a synthetic compound
related to progesterone and is sometimes used to assist weight
gain in people with cancer or AIDS; erythropoietin (EPO) is used
to treat anemia; tamoxifen may be valuable for preventing breast
cancer, osteoporosis and heart disease.

All of these are derivatives of endogenous (naturally
occurring) hormones. The scope of their abilities shows that
hormones perform an extensive array of natural functions, and
that they may become a constituent of medical therapies even in
the absence of clear endocrine dysfunction.

Secondly, and more to the point, HIV clinicians are now
treating some patients with certain hormones to directly
compensate for chronic endocrine insufficiencies which are
associated with HIV infection but do not result necessarily or
exclusively from acute opportunistic infections.

Corticosteroids

For example, doctors at Mt. Sinai Medical Center in New York
have treated HIV-associated myopathy successfully with prednisone
(Simpson DM and others, 1991). Myopathy is an inflammatory
degeneration of muscle fibers which can cause pain or tiredness
and which can resemble wasting syndrome. Unfortunately,
prednisone's capacity for quieting the inflammation also means
that it can suppress the immune system generally, or cause
hyperglycemia in some people. But Mt. Sinai clinicians did not
find this to be the case at the doses used -- beginning with 60
mg given daily, then every other day, tapering further as the
patients' myopathy was controlled.

In addition, prednisone is sometimes given orally to control
mouth sores which are related to HIV infection but not caused by
herpes, or to ease the disabling pain of HIV-associated
arthritis.

But prednisone is a powerful hormone, and the short-term
benefits should be balanced against long-term concerns. (It is
an analog of cortisone, which is produced by the adrenal cortex.)

The adrenal cortex also produces cortisol (hydrocortisone),
although insufficiently in some people with AIDS. People with
adrenal insufficiency may present with low sodium and high
potassium levels, and fatigue and weight loss that cannot be
attributed to other causes. Some experienced HIV physicians now
give cortisol to treat adrenal insufficiency in some patients.
Many patients' symptoms have improved with such treatment.
(Cortisone and cortisol are often called corticosteroids.)

Paradoxically, some Miami researchers have observed evidence
of elevated cortisol levels in the development of AIDS. Their
findings will be presented in depth at the VIII International
Conference on AIDS in July. (This may or may not be connected to
the fact that emotional depression is associated with elevated
cortisol in some people.)

Androgenic anabolic steroids

Stewart E. Springstead, M. D., contacted us after our first
report to share some of his patients' experiences with hormones
known as androgenic (male) anabolic (tissue mass- increasing)
steroids. Dr. Springstead's specialty is psychopharmacology, but
he has substantial clinical experience in his New York practice
treating some of the constitutional symptoms presented by his
patients with AIDS. In the process, he discovered that many of
his patients had testosterone levels low enough to warrant
replacement therapy, and that most were experiencing progressive
loss of body mass. Consequently, he has offered those patients a
trial of the androgenic anabolic steroid nandrolone.

According to Dr. Springstead, the benefits of nandrolone are
both physiological and psychological. Physically, there have
been general increases in muscle mass, strength, body weight and
hemoglobin. The psychological benefits include an increase in
appetite and subsequent improved nutrition, and increases in
energy, libido and feeling of well being.

Androgenic anabolics have a variable absorption rate in the
gastrointestinal tract, and they can cause minor, if reversible,
liver dysfunction when given orally. To avoid these problems,
Dr. Springstead administers the injectable nandrolone.

He believes there is no clinical evidence that androgenic
anabolic steroids, as opposed to the corticosteroids, are
immunosuppressive. In fact, he suspects, as others do, that they
may have a protective effect on the immunologic and hematopoietic
systems. After three months on androgenic anabolic therapy, one
of his patients experienced an increase in p24 antibodies, and a
reversal of p24 antigen from positive to negative.

DHEA is also an androgen, though a mild one, and contributes
to the production of testosterone. In the medical literature
DHEA has been associated with a decreased risk of heart disease
and certain cancers, a modest inhibition of the HIV and Epstein-
Barr viruses, and enhanced interleukin-2 synthesis by activated T
cells.

Because its normal levels were found to drop before
progression to AIDS, DHEA was reported by researchers in San
Francisco last year to be a potential marker, if not a treatment
itself, for HIV progression. A more recent report from Amsterdam
this year suggested the same thing (Mulder JW and others, 1992).
Whether replacing DHEA could have a therapeutic effect on HIV
progression remains a good question, even after it had been
available through community HIV buyers' clubs for several years.

Dr. Springstead feels that DHEA offers minimal anabolic
activity when compared to nandrolone.

We inquired about the masculinizing effects of androgenic
steroids on women. Dr. Springstead feels that such effects
develop slowly and are easily monitored, and that women with HIV,
unless they are pregnant, can effectively use nandrolone if they
are adequately informed about the potential side effects.

Dr. Springstead pointedly addressed the controversy
surrounding the misuse of androgenic anabolics by athletes. He
noted that these substances were widely used in the 1940s, 50s
and 60s to treat a variety of chronic infections, anemic
conditions, muscle wasting diseases, and protein deficiencies,
and to protect hematopoiesis (the formation of new blood cells)
after irradiation and chemotherapy.

But then the medical application of, and research into,
anabolic steroids virtually ceased following the 1970s notoriety
arising from the inappropriate use of steroids by athletes.
Consequently, a lot of valuable clinical data has been ignored --
data that Dr. Springstead feels could be of use now in the
treatment of HIV disease.

Finally, Dr. Springstead recommends three background texts:
Anabolic Steroids, by H. L. Krskemper, Basic and Clinical
Endocrinology, edited by F. S. Greenspan, and Depressive
Disorders and Immunity, edited by A. H. Miller. He describes the
latter as a major step toward an understanding of the complex
relationship between the psychological state of the individual
and the immune system, and how antidepressive therapy and the
anabolic steroids could have a positive impact on the course of
HIV disease.

Growth Hormone -- Study Recruiting

One of the most innovative developments in the endocrine
arena of HIV treatment concerns the use of growth factors to
counter AIDS-associated wasting syndrome.

Endogenous growth hormone is produced by the pituitary
gland, and is important for the making of new protein. For that
to happen, however, growth hormone is "mediated" by another
hormone called insulin-like growth factor-I (IGF-I). IGF-I is
manufactured by the liver and other tissues, and is a protein
itself.

Stanford University and the Palo Alto Veterans' Affairs
Hospital are now conducting a study of IGF-I to test its capacity
to reverse the muscle/weight loss and weakness which contribute
to wasting syndrome. We spoke to an investigator of the study,
endocrinologist Steven Lieberman, M. D., about the rationale of
IGF-I in the treatment of AIDS.

Dr. Lieberman explained that the goal of using such a
hormone is similar to the use of androgenic anabolics, but avoids
their side effects. In addition to reversing protein loss, IGF-I
might improve immune function. He said that so far, the
participants have tolerated the protocol well.

The study is still open for recruitment. Interested persons
should call 415/493-5000, extension 4148. It should be noted
that part of the study involves staying at the study unit for
fourteen days, and that upon completion participants will receive
$500.

Comment

We very much appreciate the clinical expertise and technical
advice that Drs. Lieberman and Springstead offered to this
update.

We understand that many physicians have misgivings about the
use of steroids, but perhaps this is an appropriate time to
reassess their value in situations where other options have been
exhausted. Steroids are obviously not appropriate for
asymptomatic HIV infection, or an alternative to accurate
diagnosis and treatment for AIDS-related infections. Also, men
and women have different hormonal systems, and may respond
differently to treatments; clearly more research is needed on the
impact of HIV on women, particularly on the endocrine system.
But it seems that the endocrine response to AIDS is frequently
wanting, and that it might be finessed to make a critical
difference for many people who every day face a lessening of
their physical and emotional being.

References

Following are some references to published endocrine/HIV
reports. For a more extensive list, see AIDS TREATMENT NEWS
#140, mentioned above.

Mulder JW, Jos Frissen, Krihnen P and others.
Dehydroepiandrosterone as predictor for progression to AIDS in
asymptomatic human immunodeficiency virus-infected men. The
Journal of Infectious Diseases, number 168, pages 413-418, 1992.

Cieslak TJ, Ascher DP, Zimmerman PA and others. Adrenal
insufficiency presenting as HIV wasting syndrome in a child:
initial successful response to megestrol. Pediat. AIDS HIV
Infect. Fetus Adoles., volume 2, number 5, pages 279-283,
October, 1991.

Lepage P, Van de Perre P, Van Vliet G, Nsengumuremyi F and
others. Clinical and endocrinologic manifestations in
perinatally human immunodeficiency virus type 1-infected children
aged 5 years or older. American Journal Dis. Child., volume
145, number 11, pages 1248-1250, November, 1991.

Simpson DM and Wolfe DE. Neuromuscular complications of HIV
infection and its treatment. AIDS, number 5, volume 8, pages
917-926, 1991.

Turner R. Deca-Durabolin and cytotoxic drugs. Acta
Endocrinologica 1985, Supplementum 271, pages 70-79.

Kopeva H. The history of anabolic steroids and a review of
clinical experience with anabolic steroids. Acta Endocrinologica
1985, Supplementum 271, pages 11-18.

Griffen HR and others. Mode of action and use of anabolic
steroids. The British Journal of Clinical Practice, volume 30,
number 1, pages 3-9, January 1976.