10, Issue 1, Spring / Summer 2004
Articles in this issue:
of Hyperprolactinemia in Patients Receiving Antipsychotics
K. Miller, M.D.
broadening of use of antipsychotics - specifically newer atypical
neuroleptics -- to treat common psychiatric disorders, including
depression, bipolar disease and behavioral disorders, medication-induced
hyperprolactinemia is an increasingly common syndrome faced
by endocrinologists, primary care physicians and psychiatrists.
Despite the high prevalence of hyperprolactinemia in patients
taking psychotropic medications, a minority of patients have
clinically significant signs and symptoms necessitating treatment.
When hyperprolactinemia results in hypogonadism, i.e. amenorrhea
and estrogen deficiency in women and testosterone deficiency
in men, replacement of gonadal steroids may be the treatment
of choice in many psychiatric patients so that effective psychiatric
medication regimens do not have to be modified.
1 - Clinical Manifestation of Hyperprolactinemia
medications cause hyperprolactinemia by blocking D2 dopamine
receptors and therefore dopamine action. Because dopamine tonically
inhibits prolactin release from the pituitary gland, medications
which decrease dopaminergic tone result in elevations of prolactin.
Hyperprolactinemia itself has not been demonstrated to directly
result in long-term health-related consequences, though it can
cause bothersome galactorrhea. However, by inhibiting gonadotropin
releasing hormone (GnRH) secretion and in turn gonadotropins
(LH and FSH), prolactin may result in gonadal steroid deficiency.
This produces estrogen deficiency in women and testosterone
deficiency in men, with consequent detrimental effects on skeletal
health and other signs and symptoms, as listed in Table 1. That
hyperprolactinemia itself is not responsible for bone loss has
been clearly demonstrated by Klibanski et al. who reported low
bone density in a group of women with hyperprolactinemic amenorrhea
in contrast to a group of eumenorrheic women with a similar
degree of prolactin elevation (1).
Although hyperprolactinemia commonly occurs with psychotropic
medication use, only a minority of patients - typically those
with hypogonadism - need to be considered for treatment. Interestingly,
the degree of elevation of prolactin does not predict the probability
of developing side effects, such that prolactin levels of greater
than 100 ng/ml are possible without side effects in some patients,
whereas others experience hyperprolactinemic sequelae with minimal
prolactin elevations. Studies have demonstrated that the prevalence
of hyperprolactinemia varies depending on the specific antipsychotic
medication. For example, risperidone use is more commonly associated
with hyperprolactinemia than with a number of other atypical
antipsychotic medications, including clozapine and olanzapine
(2-4). However, it should be noted that the development of diabetes
mellitus is a more frequent complication of some anti-psychotic
medications that do not commonly elevate prolactin. Despite
the high prevalence of hyperprolactinemia in patients receiving
antipsychotic medications, the incidence of prolactin-related
side effects is low. In patients receiving risperidone, which
has a high prevalence of hyperprolactinemia, less than 20% of
patients experience any side effects that could be attributed
to hyperprolactinemia (2).
diagnosis and treatment algorithm is provided in Figure 1. Prolactin
measurement is not necessary in all patients taking anti-psychotics.
Rather, only patients with galactorrhea or signs or symptoms
of hypogonadism -- amenorrhea in women and reduced libido, gynecomastia
and/or sexual dysfunction in men -- should be tested. Other
causes of hyperprolactinemia should be ruled out, including
pregnancy (in women), primary hypothyroidism and renal failure.
A decision regarding whether a pituitary MRI is indicated should
be based on a clinical assessment of the likelihood of the presence
of a pituitary or hypothalamic cause of the prolactin elevation
and other symptoms, such as headache. If the signs or symptoms
of the endocrinopathy pre-date the initiation of psychotropic
medication, the prolactin level is particularly high and therefore
cannot be attributed to medication use, or the patient manifests
signs or symptoms suggestive of a brain or pituitary tumor,
an MRI should be performed.
women and hypogonadal men, bone density monitoring is also indicated.
The decision as to whether symptomatic hyperprolactinemia warrants
a change in psychiatric medication should be carefully assessed
from a medical and psychiatric viewpoint, with consideration
of the risks and benefits of such a change. Hormone replacement
therapy can be safely prescribed in a majority of such patients
after consultation with the treating psychiatrist, thus avoiding
interruption of a regimen that may be critical to an individual's
psychiatric well-being. Treatment of hyperprolactinemia-related
hypogonadism in women of reproductive age and men should be
strongly considered both to prevent bone loss and enhance compliance
with psychiatric medication use, as sexual side effects, particularly,
can discourage patients from adhering to their medication regimens.
It should be noted that estrogen/progestin treatment will not
successfully treat galactorrhea and can worsen it, but explanations
and reassurance regarding its etiology is often sufficient.
When gonadal steroid replacement is contraindicated, modifying
the psychotropic medication regimen can be considered if acceptable
to the treating psychiatrist.
Dopamine agonist therapy is routinely prescribed as first-line
therapy for non-medication induced hyperprolactinemia to treat
hypogonadism or to reduce the size of a pituitary tumor. However,
dopamine agonists should be generally avoided in patients with
psychiatric disorders, as psychosis can be precipitated in an
occasional case. Dopamine agonists have sometimes been used
to lower neuroleptic-induced hyperprolactinemia (5) but should
be considered only in patients without histories of psychosis
and with extreme caution, and under the supervision of a psychiatrist.
although hyperprolactinemia is commonly caused by antipsychotic
medication use, treatment is only necessary in women of reproductive
age and men with resultant hypogonadism - a minority of those
with elevations in prolactin. After a work-up to rule out alternative
causes of hyperprolactinemia, as indicated, has been completed
and bone density measurement performed, gonadal steroid replacement
should be considered to preserve skeletal health and maintain
compliance with a successful psychiatric medication regimen.
Referral to an endocrinologist for work-up and treatment of
hyperprolactinemia is appropriate and decisions regarding any
change in psychotropic treatment regimen should be made in consultation
with the treating psychiatrist.
A, et al. J Clin Endocrinol Metab. 1988; 67(1):124-30.
2. Kleinberg DL, et al.
J Clin Psychopharmacol. 1999; 19(1):57-61.
3. Kearns AE, et al. Endocr Pract. 2000; 6(6):425-9.
4. Volavka J, et al. J Clin Psychiatry. 2004; 65(1):57-61.
5. Cavallaro R, et al. J Clin Psychiatry. 2004; 65(2):187-90.
Figure 1 (click image for pdf version).
Disease in Multiple Endocrine Neoplasia Type 1
E. Mulder, M.D.
endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome
defined by the presence of pituitary adenomas, pancreatic islet
cell tumors, and hyperparathyroidism. Other endocrine tumors
(carcinoid and adrenocortical tumors), as well as non-endocrine
tumors (lipoma, angiofibroma) may also occur as part of the
syndrome (Table 1). MEN1 occurs in 0.02-0.2 per 1000 people,
with most cases occurring as part of a familial syndrome, although
sporadic cases also occur (1). After a brief overview of the
genetics of MEN1, this review will focus on the pituitary manifestations
of the syndrome.
Larsson demonstrated by linkage analysis that the MEN1 gene
locus was located on chromosome 11q13 (2). Nine years later,
the MEN-1 gene was identified by positional cloning (3). The
protein encoded by the MEN1 gene is a 610-amino acid called
menin. Menin is a nuclear protein that interacts with several
proteins, such as JunD, Smad3, Pem, Nm23, NF-kB, replication
protein A, GFAP, and Vimentin. The exact function of menin is
unknown, but it appears to regulate cell growth and has tumor
suppressor properties (4).
germ line mutations in the MEN1 gene have been demonstrated
in the majority of familial and sporadic cases of MEN1 (3,5,6).
The reported mutations include small deletions, insertions,
nonsense mutations, missense mutations, and mRNA splicing defects,
which predict truncation or absence of the menin protein and
the propensity for tumor formation (5-7). Tumors from MEN1 patients
reveal loss of the wild-type allele (loss of heterozygosity)
or somatic point mutations of the MEN1 gene, supporting Knudsen's
two-hit model of tumorigenesis (8,9). Somatic MEN1 mutations
have also been found in sporadic tumors, including parathyroid
adenomas, gastrinomas, insulinomas, and bronchial carcinoids
(7). Although menin RNA and protein is expressed in nearly all
tissues, the absence of menin is associated primarily with tumors
of the endocrine system (10). The presence of inactivating germline
mutations in MEN1 patients, and the observation of loss of heterozygosity
or somatic mutations in MEN1 tumors, supports the hypothesis
that menin has tumor suppressor properties.
combinations of different endocrine tumors. A practical clinical
definition of MEN1, as recommended by a recent consensus panel,
is the presence of at least two of the three main endocrine
tumors (parathyroid, pancreas, pituitary) (11). Primary hyperparathyroidism
(HPT) is the most common feature of MEN1, with greater than
90% penetrence by age 50 (1,12). Duodenal or pancreatic neuroendocrine
tumors occur in 30-80% of patients with MEN1, whereas the reported
prevalence of anterior pituitary tumors is 15-50%, depending
on the patient population studied and the method of diagnosis
(1,12). Although the clinical presentation in MEN1 is quite
variable, a genotype-phenotype correlation has not been reported
1. Expressions of MEN1 with estimated penetrance
(in parentheses) at age 40 yr
NF1 including pancreatic polypeptide (20 2
Other: glucagonoma, VIPoma, somatostatinoma, etc.
Rare, maybe innate, endocrine or nonendocrine features
Thymic carcinoid NF (2%)
carcinoid NF (2%)
Other: GH+ PRL, GH, NF (each 5%)
ACTH (2%), TSH (rare)
cortex NF (25%)
1 NF, Nonfunctioning. May synthesize a peptide hormone
or other factors (such as small amine), but does
not usually oversecrete enough to produce a hormonal
2 Omits nearly 100% prevalence of NF and clinically
silent tumors, some of which are detected incidental
to pancreatico-duodenal surgery in MEN1.
[Reprinted with permission from The Endocrine Society
adenoma may be the initial presentation of disease in a subset
of patients. For example, Verges et al analyzed data from a
large series of MEN1 patients (n=334) in France and Belgium
and reported that 16.7% of patients presented with pituitary
adenoma at initial diagnosis of MEN1. Alternatively, 35.6% of
subjects initially presented with HPT and 18.8% presented with
pancreatic tumors (13). Pituitary adenomas can occur at any
age. In one series, the age of onset of pituitary adenoma in
MEN1 ranged from 12-83 years of age, although the majority of
patients were diagnosed before 50 years of age (13). The youngest
reported MEN1 patient with a pituitary macroadenoma is 5 years
of age (14). Pituitary adenomas appear to occur more frequently
in women than in men with MEN1 (13). Prolactinomas are the most
commonly occurring hormone secreting adenomas in MEN1 patients,
although growth hormone and ACTH secreting tumors, as well as
nonfunctioning tumors, also occur (13,15,16). As compared with
non-MEN1 pituitary adenomas, the age at diagnosis, the female
preponderance, and the frequency of the type of pituitary adenoma
in MEN1 are similar (13)(Table 2).
of pituitary tumors in MEN1 is based upon medical history, physical
exam, biochemical screening tests for pituitary hormones, such
as prolactin, and radiologic imaging. The clinical symptoms
and signs of pituitary adenoma are similar in patients with
MEN1 or sporadic tumors and depend upon the size and type of
the adenoma. Headache and visual field abnormalities may be
the initial clinical manifestations in those with larger tumors.
Symptoms related to prolactin-secreting adenomas include amenorrhea,
galactorrhea, and infertility in women, and diminished libido
and impotence in men. Patients with GH or ACTH secreting tumors
present with typical symptoms and signs of acromegaly or Cushing's
with symptoms of Cushing's syndrome require an initial screening
evaluation (24-hour urine free cortisol or 1-mg overnight dexamethasone
suppression test). When screening is positive, confirmatory
tests are performed. MEN1 patients with ACTH-dependent Cushing's
syndrome present the clinician with the dilemma of distinguishing
pituitary Cushing's disease from ectopic Cushing's syndrome,
secondary to an ACTH-secreting carcinoid (bronchial or mediastinal)
or pancreatic islet cell tumor, both of which can occur in the
MEN1 syndrome. However, as in the general population, a pituitary
source of excess ACTH is much more common than ectopic ACTH
production, even in MEN1 kindreds (17). For the patient with
ACTH-dependent Cushing's syndrome and a normal pituitary MRI
scan, the approach to localizing the ACTH production is the
same as in non-MEN1 patients. Specifically, bilateral inferior
petrosal sinus sampling should distinguish a central source
from an ectopic source of ACTH production in the majority of
of pituitary adenomas in MEN1 is similar to the treatment of
non-MEN1 pituitary adenomas. The goals of therapy are to reduce
tumor volume and thereby eliminate any symptoms of mass effect
(headache, visual disturbance) and to decrease hormone hypersecretion,
if evident. Treatment modalities can include surgery, radiation
therapy, or medical therapy, depending on the size and type
of tumor. However, tumor size is larger in MEN1 and successful
treatment occurs less frequently (13,15). In the series of patients
with MEN1 reported by Verges et al (13), 136 patients with MEN1-associated
pituitary adenoma were compared with 110 patients with non-MEN1
pituitary adenomas. Macroadenomas (tumor size >10 mm), including
prolactin-secreting macroadenomas, occurred more frequently
in MEN1 (85% vs 42%), regardless of the decade of diagnosis.
Using similar treatment modalities, normalization of hormone
levels in hormone-secreting tumors occurred in 90% of non-MEN1
tumors, but in only 42% of MEN1 tumors, with a median follow-up
interval of 11.4 years (Table 2) (13). Thus, pituitary tumors
in MEN1 appear to be more aggressive than non-MEN1 pituitary
tumors (13,15,18), although pituitary carcinoma has not been
linked to MEN1 (18). Successful treatment occurs more often
in patients diagnosed with microadenomas (13), which underscores
the importance of early screening and diagnosis in MEN1 kindreds.
Even after successful treatment of a pituitary adenoma, annual
monitoring should continue in order to detect recurrence (11).
screening for pituitary disease in known carriers of MEN1 is
advocated by most investigators (11,12). The MEN1 consensus
panel recommended annual biochemical screening of MEN1 carriers
for prolactinoma and acromegaly (with assessment of prolactin
and IGF-1, respectively) beginning at 5 years of age, the earliest
age at which a pituitary tumor has been reported. MRI scanning
of the pituitary was recommended at 3-year intervals. Lifetime
screening for new pituitary disease is recommended (11), as
the onset of pituitary tumors may occur late in some patients.
2. Pituitary adenomas in MEN1 patients and in controls.
(n = 136)
(n = 110)
11.1 ± 8.7
10.0 ± 6.3
of pituitary adenoma:
n = 15
n = 7
n = 2
n = 18
Clinical signs related to tumor size
= 39 (29%)
= 15 (14%)
= 19 (14%)
n = 116 (85%)
no data: n = 1 (1%)
= 64 (58%)
n = 46 (42%)
Normalization of pituitary hypersecretion
= 49 (42%)
= 83 (90%)
each qualitative data, the number of patients and
the percentage of affected patients in each group
(MEN1 patients and controls) are given. The results
of the statistical comparison between the two groups
(MEN1 patients and controls) are shown in the last
column. [Reprinted with permission from The Endocrine
to 20 percent of patients with MEN1 will develop pituitary adenomas.
Although most patients are identified by 50 years of age, pituitary
disease may also be a late manifestation of the syndrome, underscoring
the importance of lifelong screening of affected MEN1 kindreds.
The clinical presentation of pituitary adenoma is similar in
sporadic and MEN1 cases; however, patients with MEN1 tend to
have larger tumors that are less responsive to therapy. Treatment
is more successful with microadenomas compared with macroadenomas,
and therefore, early identification through biochemical screening
should improve therapeutic response.
ML, et al. Endoc Rev. 1987; 4:391-405.
2. Larsson C, et al. Nature. 1988; 332:385.
3. Chandrasekharappa SC, et al. Science. 1997; 276:404.
4. Chandrasekharappa SC, The BT. J Int Med. 2003; 253:606-15.
5. Agarawal SK, et al. Hum Mol Genet. 1997; 6:1169-75.
6. Giraud S, et al. Am J Hum Genet. 1998; 63:455-67.
7. Marx SJ, et al. Recent Prog Horm Res. 1999; 54:397-438.
8. Guru SC, et al. J Int Med. 1998; 243:433-9.
9. Pannett AAJ, Thakker RV. J Clin Endocrinol Metab. 2001;
10. Wautot V, et al Int J Cancer. 2000; 15:877-81.
11. Brandi ML, et al. J Clin Endocrinol Metab. 2001; 86:5658-71.
12. Trump D, et al. QJM. 1996; 89:653-69.
13. Verges B, et al. J Clin Endocrinol Metab. 2002; 87:457-65.
14. Stratakis CA, et al. J Clin Endocrinol Metab. 2002; 85:4776-80.
15. Burgess JR, et al. J Clin Endocrinol Metab. 1996; 81:2642-6.
16. Burgess JR, et al. J Clin Endocrinol Metab. 1996; 81:1841-5.
17. Marx SJ, et al. Ann Intern Med. 1998; 129:484-94.
18. Beckers A, et al. J Int Med. 2003; 253:599-605.
Regulation and Potential Utility of Growth Hormone in HIV Lipodystrophy
Koutkia, M.D. and Steven Grinspoon, M.D.
HIV lipodystrophy is a recently described metabolic syndrome
characterized by changes in fat distribution and insulin resistance
(1) (2) (3). Fat distribution changes are heterogeneous and
can include reduced subcutaneous fat as well as increased visceral
fat (4). In non-HIV-infected patients, obesity is associated
with reduced GH secretion (5). Johannsson et al. (6) have shown
that GH administration (0.01 mg/kg/day) to abdominally obese
men reduced visceral fat and improved glucose disposal rates.
At first glance, such a finding may seem contradictory, because
GH is known to increase insulin resistance and antagonize the
actions of insulin. However, use of low-dose GH may actually
improve insulin resistance in association with reduced visceral
adiposity. In such a scenario, the lipolytic effects might,
therefore, prevail over the diabetogenic effects of GH.
1. Potential schema for the mechanisms of reduced GH
secretion HIV lipodystrophy. [Reprinted with permission
from the American Journal of Physiology (9)].
the rationale for the use of GH in HIV-infected patients with
fat redistribution? Although the mechanisms of fat redistribution
in HIV-infected patients receiving highly active antiretroviral
therapy have not been determined, such patients often demonstrate
extreme visceral obesity without increases in total body fat.
In such patients, excess visceral fat, not total body fat, predicts
reduced GH secretion (4). Overnight GH secretion and pulse amplitude
are decreased in patients with HIV lipodystrophy (4). The physiologic
regulation of growth hormone (GH) is complex, and occurs under
the duel influence of growth hormone releasing hormone (GHRH)
and somatostatin. More recently, it has been suggested that
ghrelin, a nutritionally mediated gut peptide and GH secretogogue
(7) may also be an important regulator of GH secretion. Growth
hormone is reduced in generalized obesity and recent studies
suggest that visceral fat is a critical determinant of GH secretion
(8). Increased somatostatin tone is thought to contribute to
reduced GH secretion in obesity, but little is known regarding
the pattern of GH secretion and regulation of GH by somatostatin,
GHRH and ghrelin in lipodystrophic conditions when total fat
may be unchanged but fat distribution markedly altered. Increased
somatostatin tone, impaired GHRH stimulation of GH by excess
free fatty acids and reduced ghrelin were all recently shown
to contribute to the altered pattern of GH secretion in HIV
lipodystrophy (9) (Figure 1).
of GH has been proposed both in the treatment of AIDS wasting
to increase lean body and muscle mass, as well as in the HIV
lipodystrophy syndrome, to reduce abdominal visceral fat. Use
of the same hormone, GH, in these two seemingly disparate conditions,
highlights the multiple effects of GH. GH is anabolic, improves
nitrogen balance, and increases lean body mass. GH is also lipolytic
and may prove useful to decrease visceral fat in patients with
with AIDS wasting are undernourished and have significant GH
resistance. Clinical trials have investigated the effects of
high dose GH on lean body mass in patients with AIDS wasting.
A large randomized, placebo-controlled study of patients with
advanced HIV disease and weight loss demonstrates a significant
3-kg increase in lean body mass over 12 weeks in response to
GH (10). In this study, 178 HIV-infected patients with documented
unintentional weight loss of at least 10% or weight less than
90% of the lower limit of ideal body weight were randomly assigned
to receive either recombinant human growth hormone, 0.1 mg/kg
of body weight per day (average dosage, 6 mg/d) (n = 90) or
placebo (n = 88) for 12 weeks. No significant differences were
seen between groups in clinical events, progression of AIDS,
CD4+ or CD8+ cell counts, or viral burden. Treatment with growth
hormone increased body weight, lean body mass, and treadmill
work output (10). The dose of GH used, 0.1 mg/kg/day, was quite
high (in comparison, GH may be initiated at doses as low as
0.002 mg/kg/day for adults with GH deficiency). Although the
extracellular fluid component of fat-free mass increased, functional
indices improved, suggesting a true anabolic effect of GH. However,
significant side effects occurred in response to high dose GH,
including arthralgias, fluid retention and glucose intolerance
(10). The Food and Drug Administration (FDA) approved recombinant
human growth hormone, for treatment of AIDS-related wasting
(11), but caution is generally recommended in prescribing large
doses of GH, and this strategy is best employed for patients
with severe wasting.
a number of studies have proposed the use of GH as a lipolytic
agent in HIV-infected patients with fat redistribution (12).
GH is not approved for this indication and the use of GH for
lipodystrophy must be considered experimental. Wanke et al.
gave 6 mg of rhGH a day, subcutaneously for 12 weeks to ten
HIV-infected patients (seven men, three women) with HIV associated
lipodystrophy in order to determine the efficacy of recombinant
human GH in the treatment of the fat redistribution syndrome.
Short-term treatment improved the alterations in body shape
that occur with lipodystrophy in HIV-infected patients (12).
However, the dose used, 0.1 mg/kg/day was associated with significant
side effects including hyperglycemia.
et al. investigated GH as a potential treatment for the excess
visceral fat in HIV lipodystrophy. A prospective, open-label
trial of rhGH 6 mg/d for 24 weeks, followed by 4 mg every other
day was conducted. Thirty HIV-positive participants (26 men
and 4 women) with visceral adiposity were enrolled. The main
outcome measure was change in visceral adipose tissue (VAT)
measured by whole-body magnetic resonance imaging scan. Changes
in whole-body subcutaneous adipose tissue and skeletal muscle,
glucose metabolism, serum lipids, and quality of life were also
assessed. Despite stable body weight, VAT decreased an average
of 42% with the
6 mg/d dose and by 15% with the 4 mg q.o.d. dose after 12 weeks
(Figure 2). Subcutaneous adipose tissue also decreased, but
proportionately less and not significantly on the lower dose.
Skeletal muscle increased. Joint pain was the most common adverse
event, and was reflected in subjective quality of life measurements
as an increase in bodily pain. Insulin sensitivity fell, and
four participants developed diabetes (13).
2. Visceral adipose tissue (VAT) volume estimated
by whole body magnetic resonance imaging scans. (A) Results
from 8 subjects with evaluable scans for every visit.
(B) Results of all evaluable data at each visit. Bars
represent the standard deviation. Statistical comparisons
are by paired t tests using only subjects with evaluable
data at each compared visit. Weeks 12, 24, and 36 are
compared with baseline; weeks 48 and 60 are compared with
week 36. #p < .05; * p < .01; +p < .001. [Reprinted
with permission from JAIDS (13)].
Lo et al.
(14), conducted an open-label study to evaluate the effects
of a lower but still pharmacologic dose of GH (3 mg/d) in eight
men with HIV-associated fat accumulation. Oral glucose tolerance,
insulin sensitivity, and body composition were measured at baseline,
and one and six months. Five patients completed six months of
GH therapy. Over six months, GH reduced buffalo hump size and
excess visceral adipose tissue. Total body fat decreased, primarily
in the trunk region and lean body mass increased. One patient
with baseline-impaired glucose tolerance but a normal fasting
glucose developed fasting hyperglycemia, and an additional patient
required a dose reduction for arthralgias and developed diabetes
mellitus based on the 2-h glucose level during the oral glucose
tolerance test. Insulin sensitivity and glucose tolerance initially
worsened, but subsequently improved toward baseline. The dose
of GH used by Lo et al. was supraphysiologic and resulted in
an increase in IGF-I levels up to three times the upper normal
range (14). In contrast to high dose GH, low-dose GH might improve
insulin resistance in association with reductions in visceral
fat. Normally nourished HIV patients with excess visceral fat
demonstrate decreased GH secretion without GH resistance, suggesting
that lower doses of GH may be efficacious in this population.
Further studies are necessary to address these possibilities.
use of high dose GH increases muscle mass in patients with AIDS
wasting. Care should be exercised in utilizing this therapy,
which is best reserved for those with severe wasting, refractory
to other therapies. The optimal dose is not known and monitoring
for side effects is critical. More recent studies suggest the
potential use of GH in patients with HIV lipodystrophy and excess
visceral fat, in whom GH levels are reduced. GH is effective
in reducing visceral fat but may aggravate insulin resistance
and hyperglycemia at high doses. GH is not approved for use
in HIV lipodystrophy and should not be used in patients with
lipodystrophy other than in approved clinical studies with appropriate
monitoring. Further studies are needed to define the optimal
dose, duration of dosing, and subpopulation of HIV-infected
patients most likely to benefit from GH.
A, et al. AIDS. 1998;12(7):F51-8.
2. Hadigan C, et al. JAMA 2000; 284(4):472-7.
3. Grinspoon S, et al. Clin Inf Dis. 2003; 36(Suppl 2):S69-78.
4. Rietschel P, et al. J Clin Endocrinol Metab. 2001; 86(2):504-10.
5. Veldhuis JD, et al. J Clin Endocrinol Metab. 1991; 72(1):51-9.
6. Johannsson G, et al. J Clin Endocrinol Metab. 1997; 82(3):727-34.
7. Kojima M, et al. Nature. 1999; 402(6762):656-60.
8. Clasey JL, et al. J Clin Endocrinol Metab. 2001; 86(8):3845-52.
9. Koutkia P, et al. Am J Physiol Endocrinol Metab. 2004;
10. Schambelan M, et al. Ann Intern Med. 1996; 125(11):873-82.
11. James J. AIDS Treat News. 1996; Sep 6;(No 254):1-4.
12. Wanke C, et al. AIDS. 1999; 13(15):2099-103.
13. Engelson ES, et al. J Acquir Immune Defic Syndr. 2002;
14. Lo JC, et al. J Clin Endocrinol Metab. 2001; 86(8):3480-7.
may qualify for research studies in the Neuroendocrine Clinical
Center. We are currently accepting the following categories
of patients for screening to determine study eligibility. Depending on the study, subjects may receive
free testing, medication and/or stipends.
diagnosed acromegaly patients
preoperative medical treatments
with acromegaly requiring medical therapy
several different medical therapies
Beverly M.K. Biller
with Cushing’s Syndrome
a potential new medical therapy
Beverly M.K. Biller
with history of cured acromegaly and current hypopituitarism
GH effects in patients with history of cured acromegaly
and GH deficiency
with hypopituitarism (panhypopituitary or partial hypopituitarism)
Beverly M.K. Biller
Karen K. Miller
with anorexia nervosa
Karen K. Miller
girls with anorexia nervosa
bone density and the effects of estrogen replacement
with hypopituitarism, ages 18-50
replacement therapy study
Karen K. Miller
positive women with weight loss or fat redistribution
of bone loss
of cardiovascular risk markers
positive men and women with fat redistribution
treatments to redistribute fat
of GH levels and efficacy of GH secretogogues
lipid lowering therapy
Tax deductible contributions
can made to the Neuroendocrine Clinical Center to support educational
endeavors and clinical research activities. Please contact Ruth
Nally at 617-726-3897 for further information
& Pituitary Center |
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