ORIGINAL
ARTICLE
ENDOCRINOPATHY
IN POEMS SYNDROME
Endocrinopathy in POEMS Syndrome:
The Mayo Clinic Experience
GUNJAN Y. GANDHI, MD, MSC; RITA BASU, MD; ANGELA DISPENZIERI, MD; ANANDA BASU, MD;
VICTOR M. MONTORI, MD, MSC; AND MICHAEL D. BRENNAN, MD
OBJECTIVE: To determine the prevalence and characteristics of
endocrinopathies at diagnosis of POEMS (p olyneuropathy,
organomegaly, endocrinopathy, M protein, and skin changes)
syndrome.
PATIENTS AND METHODS: From January 1, 1960, through June 30,
2006, we identified 170 patients with POEMS syndrome in the
Mayo Clinic dysproteinemia database. We abstracted information
about endocrine abnormalities from their medical records.
RESULTS: Of the 170 patients with POEMS syndrome during the
entire study period, the 64 patients seen after 2000 had more
complete endocrine evaluations; of these 64 patients, 54 (84%)
had a recognized endocrinopathy (38 men; median age, 50 years;
interquartile range, 43-59 years). Hypogonadism was the most
common endocrine abnormality; 26 (79%) of 33 men had subnormal total testosterone levels, and 10 men had gynecomastia.
Among the 35 patients with measured prolactin levels, 7 men and
3 women had elevated levels. Hypothyroidism was noted in 17
men and 11 women. Abnormalities in glucose metabolism were
present in 24 (48%) of 50 patients; 16 patients had impaired
fasting glucose levels, and 8 were diagnosed as having diabetes.
Adrenal insufficiency (defined by an abnormal response of cortisol
to stimulation with standard high-dose [250 µg] synthetic adrenocorticotropic hormone) was noted in 6 of 9 patients tested.
Fourteen (27%) of 51 patients tested had hypocalcemia. Twentynine (54%) of 54 patients had evidence of multiple endocrinopathies in the 4 major endocrine axes (gonadal, thyroid, glucose,
and adrenal).
CONCLUSION: The high prevalence of endocrinopathy in our study,
to our knowledge the largest published series of POEMS cases,
calls for a thorough endocrine investigation in patients presenting
with this syndrome.
Mayo Clin Proc. 2007;82(7):836-842
ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; POEMS = polyneuropathy, organomegaly, endocrinopathy, M
protein, and skin changes; PTH = parathyroid hormone; VEGF = vascular
endothelial growth factor
I
n 1980, Bardwick et al1 coined the acronym POEMS to
represent a rare multisystem syndrome characterized by
polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes. Two major criteria and at least 1
minor criterion should be satisfied to differentiate this syndrome from neuropathy associated with monoclonal
gammopathy of undetermined significance, myeloma, primary systemic amyloidosis, and Waldenström disease. The
major criteria include polyneuropathy and a clonal plasma
proliferative disorder (almost always λ). The minor criteria
include osteosclerotic bone lesions; Castleman disease;
papilledema; organomegaly, including lymphadenopathy;
836
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•
edema, pleural effusion, or ascites; endocrinopathy; and
skin changes.2 Individual patients may have some or all of
the features at the time of diagnosis or during follow-up.
Syndrome synonyms include osteosclerotic myeloma,
Crow-Fukase syndrome, Takatsuki syndrome, or plasma
cell dyscrasia, endocrinopathy, and polyneuropathy.3,4
Although a detailed understanding of the pathogenesis
is lacking, increased levels of cytokines, particularly vascular endothelial growth factor (VEGF), are a common
finding and may play an important role in the disorder.5-7
Vascular endothelial growth factor is a growth factor for
endothelial cells that induces an increase in vascular permeability, is important in angiogenesis, and often decreases with successful therapy.8-11
Peripheral neuropathy is the dominant and frequently
the presenting symptom. Because the characteristics of the
neuropathy are similar to those of chronic inflammatory
demyelinating polyneuropathy, patients are frequently
misdiagnosed as having chronic inflammatory demyelinating polyneuropathy or monoclonal gammopathy of undetermined significance–associated peripheral neuropathy.
Not until additional features of the POEMS syndrome are
recognized is the correct diagnosis made and effective
therapies initiated.
Endocrinopathy is a central feature of POEMS syndrome. Several hormonal disorders have been described,
including hypogonadism, diabetes mellitus, hypothyroidism, hyperprolactinemia, adrenal insufficiency, gynecomastia in men, breast engorgement in women, hyperestrogenemia, and hypoparathyroidism.1-3,12-14 The cause of
endocrinopathies is unknown. Circulating antibodies directed against hormones or specific hormone receptors
have not been found.1 At autopsy, endocrine glands appear
From the Division of Endocrinology, Diabetes, Metabolism, and Nutrition (G.Y.G.,
R.B., A.B., V.M.M., M.D.B.), Knowledge and Encounter Research Unit (G.Y.G.,
V.M.M.), and Division of Hematology (A.D.), Mayo Clinic, Rochester, Minn.
Data were presented in part at the Endocrine Society’s 86th Annual Meeting;
New Orleans, La; June 16-10, 2004; and at the Endocrine Society’s 89th
Annual Meeting; Toronto, Ontario; June 2-5, 2007.
Individual reprints of this article are not available. Address correspondence to
Gunjan Y. Gandhi, MD, MSc, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (email: gandhi.gunjan@mayo.edu).
© 2007 Mayo Foundation for Medical Education and Research
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ENDOCRINOPATHY IN POEMS SYNDROME
structurally normal and without defining characteristics.15
Therefore, it seems likely that the endocrine abnormalities
reflect a functional rather than structural disturbance of
gland function.
Most of the information regarding endocrinopathies in
POEMS syndrome is from isolated case reports or small
case series that have not systematically studied the various
endocrine manifestations in this disorder. To take advantage of our institution’s experience with a large series
of patients, we sought to determine the prevalence and
characteristics of endocrinopathies at diagnosis of POEMS
syndrome to further our understanding of this enigmatic
disorder.
TABLE 1. Criteria for Diagnosis of POEMS Syndrome2*
Criteria type
Major
Minor
Known
associations
PATIENTS AND METHODS
All patients with POEMS syndrome who met minimal
criteria for inclusion in the study were identified through
the Mayo Clinic dysproteinemia database.2 From January
1, 1960, through June 30, 2006, 170 patients (115 previously described2,16) met both major criteria and 1 minor
criterion for the diagnosis of POEMS syndrome (Table 1).
Because of the high prevalence of diabetes mellitus and
thyroid abnormalities, these diagnoses alone were not sufficient to meet the minor criterion. Using a standardized
data extraction form, we abstracted information from the
medical records of these patients regarding their endocrine
abnormalities at the time of diagnosis of POEMS syndrome. Diabetes mellitus and hypothyroidism were not
attributed to POEMS syndrome unless these reportedly
occurred months to years after the onset of at least another
feature of POEMS syndrome.
As we conducted our investigation, we noticed a difference in the extent of endocrine evaluation over time.
Patients seen before 2000 had few endocrine tests, particularly when they had no endocrine-related symptoms. Conversely, patients seen in 2000 or later had a more complete
endocrine evaluation. Thus, we decided to focus our results
on the subset of patients seen in 2000 or later. The Mayo
Foundation Institutional Review Board approved the study
in accordance with Minnesota state law that regulates research from medical records.
RESULTS
Of the 170 patients with POEMS syndrome, 106 were
treated before 2000, and 64 were treated in 2000 or later
(Table 2). A total of 118 patients (69%; 95% confidence
interval, 62%-76%) had a recognized endocrinopathy (89
men; median age, 54 years, interquartile range, 47-63
years). Fifty-four (84%) of the 64 patients treated in 2000
or later (95% confidence interval, 73%-92%) had a recogMayo Clin Proc.
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Possible
associations
Description
Polyneuropathy
Monoclonal plasma proliferative disorder
Sclerotic bone lesions†
Castleman disease†
Organomegaly (splenomegaly, hepatomegaly, or
lymphadenopathy
Edema (pleural effusion or ascites)
Endocrinopathy (adrenal, thyroid,‡ pituitary,
gonadal, parathyroid, pancreatic‡)
Skin changes (hyperpigmentation, hypertrichosis,
plethora, hemangiomata, white nails)
Papilledema
Clubbing
Weight loss
Thrombocytosis
Polycythemia
Hyperhidrosis
Pulmonary hypertension
Restrictive lung disease
Thrombotic diatheses
Arthralgias
Cardiomyopathy (systolic dysfunction)
Fever
Low vitamin B12 values
Diarrhea
*Two major criteria and at least 1 minor criterion are required for diagnosis. POEMS = polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.
†Osteosclerotic disease or Castleman disease is usually present.
‡Because of the high prevalence of diabetes mellitus and thyroid abnormalities, these diagnoses alone are not sufficient to meet this minor criterion.
From Blood,2 with permission.
nized endocrinopathy (median age, 50 years; interquartile
range, 43-59 years; 38 men).
GONADAL AXIS
Hypogonadism was the most common endocrine abnormality. Thirty-three (87%) of 38 men had testosterone
levels measured; 26 (79%) had levels below the lower limit
of the normal range for total testosterone. Twenty-five
(96%) of these 26 patients had estimation of free testosterone levels performed as well, which showed low levels in
all cases. Twenty-three (61%) of 38 men reported erectile
dysfunction. In 23 men with available data, 7 (30%) had
evidence of primary hypogonadism, whereas 16 (70%) had
secondary hypogonadism. Ten men (43%) had gynecomastia, of whom only 1 had elevated estrogen levels (of the 4
men in whom estrogen levels were measured).
PROLACTIN AXIS
Among the 35 patients with measured prolactin levels, 10
(29%; 7 men and 3 women) had levels higher than the upper
limit of the normal range. In most cases, prolactin concentrations were noted to be mildly elevated. Two women had
irregular menses, 1 of whom also had galactorrhea.
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837
ENDOCRINOPATHY IN POEMS SYNDROME
TABLE 2. Endocrine Abnormalities in the Recent Cohort
(2000-2006)*†
No. (%) of patients
(N=64)
Characteristic
Patients with endocrinopathy
M/F
Median age (y) (IQR)
Race
White
Hispanic
African American
Mean body mass index (SD)
Erectile dysfunction
Hypogonadism (men)
Gynecomastia (men)
Hyperprolactinemia
Hypothyroidism
Glucose intolerance
Adrenal insufficiency
Hypocalcemia
Evidence of multiple endocrine abnormalities
54 (84)
38/16
50 (43-59)
48
5
1
25 (4)
23/38 (61)
26/33 (79)
10/38 (26)
10/35 (29)
28/48 (58)
24/50 (48)
6/9 (67)
14/51 (27)
29/54 (54)
*Data are number (percentage) of patients unless otherwise indicated.
IQR = interquartile range.
†Reference ranges for plasma, serum, or blood concentrations are as
follows: thyrotropin, 0.3 to 5.0 mIU/L; free thyroxine, 0.8 to 1.8 ng/dL;
fasting glucose, 70 to 100 mg/dL; calcium, 8.9 to 10.1 mg/dL; phosphorus, 2.5 to 4.5 mg/dL; morning cortisol, 7 to 25 µg/dL; adrenocorticotropic hormone, 10 to 60 pg/mL; total testosterone, 240 to 950 ng/dL; free
testosterone, 9 to 30 ng/dL; and prolactin, 4 to 23 ng/mL for males and 4
to 30 ng/mL for females.
THYROID AXIS
Elevated thyrotropin concentrations were noted in 28
(58%) of 48 patients (17 men and 11 women). Half of these
patients (14/28) had mild increases in thyrotropin levels
(>5 but <10 mIU/L; reference range, 0.3-5.0 mIU/L), with
most having normal free thyroxine levels, suggestive of
subclinical hypothyroidism. The other half of the patients
(14/28) had overt hypothyroidism.
GLUCOSE METABOLISM
Abnormalities in glucose metabolism were present in 24
(48%) of 50 patients; 16 had impaired fasting glucose
levels. Eight patients were diagnosed as having diabetes,
5 of whom were treated with oral agents and 3 with
insulin.
ADRENAL AXIS
Adrenal insufficiency (defined by an abnormal response of
cortisol to stimulation with standard high-dose [250 µg]
synthetic adrenocorticotropic hormone [ACTH]) was
noted in 6 (67%) of 9 patients tested. Thirteen (48%) of 27
individuals had elevated ACTH levels; 7 of these had normal morning cortisol levels.
CALCIUM REGULATION
Seventeen (33%) of the 51 patients who were tested had
low calcium levels. After correcting calcium levels for
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low albumin, 14 (27%) of 51 patients had true hypocalcemia. Parathyroid gland dysfunction was not routinely
determined. Of those with low calcium levels, 2 of 6 patients tested had high parathyroid hormone (PTH) levels
suggestive of secondary hyperparathyroidism. Two patients with measured calcium levels had hypercalcemia,
neither of whom had PTH levels measured. Phosphorus
levels were elevated in 12 (36%) of 33 patients. One of
the 64 patients had a low PTH level with a normal calcium
concentration.
MULTIPLE AXES
Twenty-nine (54%) of 54 patients had evidence of multiple
endocrinopathies in the 4 major endocrine axes (gonadal,
thyroid, glucose, and adrenal).
DISCUSSION
KEY FINDINGS
Our series of patients with POEMS syndrome, to our
knowledge the largest reported in the literature, confirms
that endocrinopathy is a central feature of this disorder.
Hypogonadism in men is the most common endocrine abnormality, whereas hypothyroidism and abnormalities of
glucose metabolism were frequently noted at the time of
diagnosis of POEMS syndrome. Of interest is the isolated
elevation of ACTH levels noted in these patients (presumed to be responsible for skin hyperpigmentation, but a
clear correlation could not be established from these data).
Also, adrenal insufficiency and hypocalcemia, which have
been infrequently reported in association with POEMS
syndrome, may be more common than previously thought.
The high prevalence of endocrinopathies calls for a thorough and systematic endocrine evaluation in patients with
POEMS syndrome.
COMPARISON WITH OTHER PUBLISHED SERIES OF PATIENTS
We compared the prevalence of endocrinopathies with
other reported series of patients with POEMS syndrome3,12 (Table 3). Because all series are retrospective
and symptoms accumulate over time, the prevalence of
each of the endocrine disorders varies. Our series reports similar numbers of patients with hypogonadism,
fewer patients with gynecomastia, and more patients
with hypothyroidism and abnormalities in glucose metabolism. Single case reports have described adrenal insufficiency14 and hypocalcemia,13 but we noted that a
significant proportion of patients who were tested for
either of these conditions had them. Although asthenia
and skin hyperpigmentation are common in POEMS syndrome, clinicians have rarely tested patients for adrenal
insufficiency.
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ENDOCRINOPATHY IN POEMS SYNDROME
TABLE 3. Clinical Characteristics of Our Study Patients Compared With 2 Previous Series*
Recent cohort
(2000-2006)
(N=64)
Nakanishi et al3
(N=102)
Soubrier et al12
(N=25)
54 (84)
38/16
50 (median) (43-59)
NR
69/33
46 (mean)
NR
17/8
51 (mean)
NR
Characteristic
Patients with endocrinopathy
M/F
Median or mean age (y) (IQR)
Race
White
Hispanic
African American
Japanese
Erectile dysfunction
Gynecomastia
Hyperprolactinemia
Hypothyroidism
Glucose intolerance
Adrenal insufficiency
Evidence of multiple endocrine abnormalities
48
5
1
23/38
10/38 (men only)
10/35
28/48
24/50
6/9
29/54
102
39/50
43/63
NR
NR
26/93
NR
NR
13/13
10/13
4/17
10/22
9/22
NR
NR
*Data are number (percentage) of patients unless otherwise indicated. IQR = interquartile range; NR = not
reported.
Adapted from Blood,2 with permission.
CAUSE OF ENDOCRINOPATHIES
The cause of POEMS syndrome is unknown. Although the
high prevalence of λ light chains (>95% of cases) is suggestive of a key role in the pathogenesis, histopathologic
review of affected organs and nerves does not support that
it is a form of deposition disorder.3,17 Antibodies to human
herpesvirus were reported in 78% of patients who have
POEMS syndrome with Castleman disease and 22% of
those with POEMS syndrome without Castleman disease.18
No circulating antibodies against hormones or hormone
receptors seem to be present.1,12 No characteristic findings
are seen in endocrine organ studies at autopsy.15
Considerable interest has been demonstrated in the role
of cytokines (chiefly interleukin 1β, interleukin 6, and
tumor necrosis factor α) as mediators of POEMS syndrome.5,19 The site of activation of the cytokine network is
not yet known, but macrophages, not T cells, are assumed
to be activated. Compared with patients with multiple myeloma, patients with POEMS syndrome had higher serum
levels of proinflammatory cytokines (interleukin 1β, tumor
necrosis factor α, and interleukin 6) and lower levels of an
antagonistic cytokine (transforming growth factor β1),
suggesting a loss of balance between proinflammatory and
anti-inflammatory cytokines.5 Vascular endothelial growth
factor is the leading candidate as a pathogenic factor in
POEMS syndrome and often decreases with successful
treatment.8-10 Also, VEGF plays a critical role in angiogenesis.11 One might hypothesize that overexpression of
VEGF in POEMS syndrome might affect several of the
endocrine axes because of a disruption of the local balance
of angiogenic factors that appears to be important in the
regulation of hormone secretion in many endocrine glands.
Because dopamine agonists disrupt VEGF signaling, these
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agents might have a role in the treatment of the endocrine
manifestations of POEMS syndrome.11 Interestingly, prolactin levels were elevated in several of our patients. Thus,
VEGF could potentially account for organomegaly, skin
lesions, edema, and possibly polyneuropathy and endocrinopathies in POEMS syndrome.
Many of the endocrine abnormalities seen in patients
with POEMS syndrome could be due to chronic illness or
illnesses commonly observed in this age population. Unfortunately, no studies have assessed endocrinopathies in
patients with POEMS syndrome compared with an ageand sex-matched population or patients with chronic disease. Although previous studies have compared cytokines5
and VEGF8 levels in patients with POEMS syndrome to
other causes of polyneuropathy (multiple myeloma, chronic inflammatory demyelinating polyneuropathy), they did
not specifically report on endocrine laboratory or clinical
abnormalities. As indicated in Table 4, the prevalence of
hypogonadism, diabetes, and hypothyroidism is significantly greater in patients with POEMS syndrome compared with population-based longitudinal cohorts.20-22
HYPOGONADISM
We confirmed the high prevalence of hypogonadism in
patients with POEMS syndrome.2,3,12 Hypogonadism was
secondary (hypogonadotropic hypogonadism) in most
cases. In comparison, Soubrier et al12 reported an equal
incidence of primary (hypergonadotropic hypogonadism)
(5/9) and secondary (4/9) hypogonadism in these patients.
In our series, a significant proportion of men who did not
report erectile dysfunction had low testosterone levels. We
also noted gynecomastia in men and irregular menses in
women, which others have described.1,3,12
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839
ENDOCRINOPATHY IN POEMS SYNDROME
TABLE 4. Prevalence of Common Endocrine Disorders in the General Population
Compared With POEMS Syndrome20-22*
Prevalence (%)
General population
Endocrine disorder
Hypogonadism
Diabetes (diagnosed)
Impaired fasting glucose
Hypothyroidism
(clinical plus subclinical)
Overall
Men
Women
Patients with
POEMS syndrome
6.6 (40-59 y)
29.9
12 (50-59 y)
7.5 (40-59 y)
37.2
5.7 (40-59 y)
22.9
79
16
32
4.6
58
*POEMS = polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.
Although estrogen was not routinely checked in our
patients, other investigators have proposed hyperestrogenemia as a unifying hypothesis for endocrinopathy.23 In
those patients, an accelerated conversion of androgens into
estrogens was found. Increased estrogen could potentially
also cause hyperprolactinemia either directly or by modifying the estrogen-testosterone ratio.24
The cause of hyperprolactinemia remains unclear. An
increased intracranial pressure in patients with POEMS
syndrome may result in disturbed hypothalamic function,
loss of inhibitory dopaminergic pathways, and hyperprolacteinemia.1 Although hyperprolactinemia may cause
hypogonadism, normalization of prolactin with bromocriptine had no effect on androgen and gonadotropin levels.1 Treatment of hypothyroidism when present did not
resolve the hyperprolactinemia. Also, 2 eugonadal men
with POEMS syndrome were noted to have primary follicle-stimulating hormone (FSH) hypersecretion, suggesting that primary FSH hypersecretion in the absence of
primary testicular failure should be added to the list of
endocrinopathies of POEMS syndrome.25 An isolated elevation of FSH levels with normal levels of FSH and
testosterone can also occur in Sertoli cell–only syndrome,
which has a wide variety of causes, including antineoplastic therapy with radiation and chemotherapy. It is not
routine practice at our institution to obtain fertility data,
perform sperm analyses, or consider cryopreservation
of sperm before chemotherapy or radiotherapy in these
patients.
GLUCOSE ABNORMALITIES
An abnormality in glucose metabolism was a common
endocrine manifestation in our series, a finding that is
consistent with previously reported large series.2,3,12 Most
patients have impaired fasting glucose levels and need
lifestyle interventions. Patients with diabetes tend to have
modest insulin requirements.1 Antibodies to pancreatic islet cells were not demonstrated in 2 patients with POEMS
syndrome.1 Potential confounders to the high incidence of
glucose abnormalities to remember are the increased fre840
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quency of impaired fasting glucose levels and diabetes
mellitus in the general population, the number of patients
with POEMS syndrome taking corticosteroids at diagnosis,
and stress hyperglycemia from severe illness. We established a clear temporal relationship between glucose intolerance and POEMS syndrome and ruled out corticosteroid
use at the time of testing in our series of patients.
HYPOTHYROIDISM
After carefully establishing that at least 1 of the features of
POEMS syndrome preceded hypothyroidism months to
years after the onset of hypothyroidism, we noted that a
significant proportion of patients had hypothyroidism.
Most patients had mild primary hypothyroidism, which
is consistent with other reports.1,2,12,13,26,27 Interestingly,
Soubrier et al described secondary (central) hypothyroidism in 2 of 10 patients with hypothyroidism in their series
of 25 patients. Although the cause remains elusive, specific
antibody-binding activity directed against pituitary tissue
was demonstrated in a patient with POEMS syndrome and
hypothyroidism.28 However, the thyrotropin levels were
high. Thyroid microsomal antibodies or thyroglobulin antibodies have not been found.1
ADRENAL INSUFFICIENCY
Adrenal insufficiency has been described infrequently in
patients with POEMS syndrome.2,14,26 We noted an abnormal ACTH stimulation test result in most of those tested.
However, data are insufficient to comment on whether this
was primary or secondary adrenal insufficiency. Previous
case reports describing adrenal insufficiency in this disorder have noted it to be a primary adrenal disorder,14,26 but
none measured adrenal autoantibodies. Bardwick et al1 did
not detect circulating inhibitors of ACTH in the serum of
the 2 patients described. The isolated elevation in ACTH
levels with a normal cortisol level (seen in 7 of 13 patients)
could indicate “compensated” cortisol levels; the fact that
we saw this in more than half the patients tested (7/13)
indicates that this is unlikely to be attributable to assay or
biological variability.
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ENDOCRINOPATHY IN POEMS SYNDROME
CALCIUM ABNORMALITIES
Although experts have not associated calcium abnormalities to POEMS syndrome, we noted that approximately
one third of patients in our series had low calcium levels.
Although parathyroid function was not routinely measured
in these patients, no evidence was available of primary
hypoparathyroidism in those cases in which PTH levels
were measured. To our knowledge, there has been only 1
report of established primary hypoparathyroidism (low
calcium, high phosphate, and undetectable PTH levels)
in association with vitamin D deficiency.13 Another case
report described a patient with hypocalcemia, hyperphosphatemia, low-normal vitamin D levels, and an inappropriately normal PTH level, suggestive of an abnormal parathyroid response.26 Routine measurement of calcium and
phosphate levels and, if abnormal, measurement of PTH,
creatinine, and vitamin D levels may be prudent. Interestingly, Nakanishi et al3 reported hypercalcemia in 7 of 23
patients, although it is unclear if this was accurate because
none had a serum calcium level greater than 10 mg/dL. The
elevated phosphate levels in our patients suggest impaired
renal function or increased bone loss of calcium and phosphate as possible mechanisms.
STUDY LIMITATIONS
Overall, the prevalence of endocrinopathy in our series is
likely an underestimate because most patients, especially
those seen before the turn of the century, had incomplete
endocrine evaluations. To enable us to gain a better understanding of asymptomatic endocrine laboratory changes
seen early in the disease, we separately studied and describe patients seen in the last 6 years, who appear to be
better characterized. This was a retrospective medical
record review with all its inherent biases. Thus, no standardized means were available for ensuring when and what
laboratory tests were performed and if they were necessarily repeated to confirm an abnormal test result. Cortisol,
testosterone, glucose, and prolactin samples were in most
cases obtained in the early morning. Because this is an
extremely rare disorder, a retrospective review has been the
preferred method of study until now. Most of the patients
seen at our institution were white. This is an extension of
the first large North American patient population reported,2
but with an emphasis on endocrine findings. We have no
follow-up information regarding progression of endocrine abnormalities or new development of endocrine disorders. However, in the future, we plan to develop a systematic method to track and obtain follow-up information
on these patients. Although we believe that this report is
helpful in guiding the evaluation today, future knowledge
about the natural history of endocrinopathies in POEMS
syndrome may be particularly helpful to the frontline cliniMayo Clin Proc.
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TABLE 5. Suggested Endocrine Review of Systems and
Laboratory Tests During Initial Evaluation of POEMS Syndrome*
Endocrine
axis
Thyroid
Glucose
metabolism
Gonadal
Prolactin
Adrenal
Calcium
regulation
Review of systems
Initial laboratory tests
Change in energy level
Skin and hair changes
Menstrual irregularities
Heat or cold intolerance
Change in bowel habits
Weight change
Mood changes
Polyuria
Polydipsia
Polyphagia
Weight change
Change in libido
Erectile dysfunction
Menstrual irregularities
Thyrotropin, free thyroxine
Gynecomastia
Galactorrhea
Breast engorgement
Menstrual irregularities
Headaches
Visual changes
Weight change
Change in energy level
Skin color changes
Salt craving
Muscle aches
Paresthesias
Muscle cramps
Fasting glucose (early
morning)
Total and bioavailable
testosterone (early
morning), FSH, luteinizing
hormone, estradiol (in
women)
Prolactin (early morning)
Cortisol, ACTH (early
morning)
Calcium
*ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hormone; POEMS = polyneuropathy, organomegaly, endocrinopathy, M
protein, skin changes.
cian following up these patients over time, especially after
treatment.
SUGGESTED APPROACH TO EVALUATING ENDOCRINOPATHIES IN
POEMS SYNDROME
We suggest that all patients with POEMS syndrome have a
thorough and systematic endocrine evaluation at diagnosis
of this syndrome. Clinicians should complete an endocrine
review of systems during the initial evaluation and obtain
total and bioavailable testosterone, prolactin, fasting glucose, cortisol and ACTH specimens (all early morning) and
thyrotropin and calcium specimens (Table 5). An endocrinologist should see patients with concerns or abnormal
levels for further assessment and treatment.
FUTURE DIRECTIONS
To gain a better understanding of the pathogenesis of endocrinopathies in POEMS syndrome, researchers should focus on studies that assess the role of cytokines and VEGF,
especially related to endocrine dysfunction. Whether endocrine disorders associated with POEMS syndrome improve
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841
ENDOCRINOPATHY IN POEMS SYNDROME
after successful treatment of the disease is unknown. Follow-up studies to better understand the evolution of endocrine disorders in these patients are needed.
CONCLUSION
The high prevalence of endocrinopathies in our study, to
our knowledge the largest published series of POEMS
cases, calls for a thorough endocrine investigation in patients who present with this syndrome and vigilance in
monitoring for treatable hormonal disorders that may
emerge during the disease.
We are grateful to Rebecca Bahn, MD, for contributing to our
reporting of the potential association between VEGF overexpression and endocrine manifestations in patients with POEMS
syndrome.
REFERENCES
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