Endocrinopathy in POEMS Syndrome: The Mayo Clinic Experience
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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 edema, pleural effusion, or ascites; endocrinopathy; and
endocrinopathies at diagnosis of POEMS (p olyneuropathy,
organomegaly, endocrinopathy, M protein, and skin changes) skin changes.2 Individual patients may have some or all of
syndrome. the features at the time of diagnosis or during follow-up.
PATIENTS AND METHODS: From January 1, 1960, through June 30, Syndrome synonyms include osteosclerotic myeloma,
2006, we identified 170 patients with POEMS syndrome in the Crow-Fukase syndrome, Takatsuki syndrome, or plasma
Mayo Clinic dysproteinemia database. We abstracted information cell dyscrasia, endocrinopathy, and polyneuropathy.3,4
about endocrine abnormalities from their medical records.
Although a detailed understanding of the pathogenesis
RESULTS: Of the 170 patients with POEMS syndrome during the is lacking, increased levels of cytokines, particularly vas-
entire study period, the 64 patients seen after 2000 had more
complete endocrine evaluations; of these 64 patients, 54 (84%) cular endothelial growth factor (VEGF), are a common
had a recognized endocrinopathy (38 men; median age, 50 years; finding and may play an important role in the disorder.5-7
interquartile range, 43-59 years). Hypogonadism was the most Vascular endothelial growth factor is a growth factor for
common endocrine abnormality; 26 (79%) of 33 men had subnor-
mal total testosterone levels, and 10 men had gynecomastia. endothelial cells that induces an increase in vascular per-
Among the 35 patients with measured prolactin levels, 7 men and meability, is important in angiogenesis, and often de-
3 women had elevated levels. Hypothyroidism was noted in 17 creases with successful therapy.8-11
men and 11 women. Abnormalities in glucose metabolism were
present in 24 (48%) of 50 patients; 16 patients had impaired Peripheral neuropathy is the dominant and frequently
fasting glucose levels, and 8 were diagnosed as having diabetes. the presenting symptom. Because the characteristics of the
Adrenal insufficiency (defined by an abnormal response of cortisol neuropathy are similar to those of chronic inflammatory
to stimulation with standard high-dose [250 µg] synthetic adreno-
corticotropic hormone) was noted in 6 of 9 patients tested. demyelinating polyneuropathy, patients are frequently
Fourteen (27%) of 51 patients tested had hypocalcemia. Twenty- misdiagnosed as having chronic inflammatory demyelinat-
nine (54%) of 54 patients had evidence of multiple endocrinopa- ing polyneuropathy or monoclonal gammopathy of unde-
thies in the 4 major endocrine axes (gonadal, thyroid, glucose,
and adrenal). termined significance–associated peripheral neuropathy.
CONCLUSION: The high prevalence of endocrinopathy in our study,
Not until additional features of the POEMS syndrome are
to our knowledge the largest published series of POEMS cases, recognized is the correct diagnosis made and effective
calls for a thorough endocrine investigation in patients presenting therapies initiated.
with this syndrome.
Endocrinopathy is a central feature of POEMS syn-
Mayo Clin Proc. 2007;82(7):836-842 drome. Several hormonal disorders have been described,
ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hor-
including hypogonadism, diabetes mellitus, hypothyroid-
mone; POEMS = polyneuropathy, organomegaly, endocrinopathy, M ism, hyperprolactinemia, adrenal insufficiency, gyneco-
protein, and skin changes; PTH = parathyroid hormone; VEGF = vascular
endothelial growth factor
mastia in men, breast engorgement in women, hyperes-
trogenemia, and hypoparathyroidism.1-3,12-14 The cause of
endocrinopathies is unknown. Circulating antibodies di-
rected against hormones or specific hormone receptors
I n 1980, Bardwick et al1 coined the acronym POEMS to
represent a rare multisystem syndrome characterized by
polyneuropathy, organomegaly, endocrinopathy, M pro-
have not been found.1 At autopsy, endocrine glands appear
tein, and skin changes. Two major criteria and at least 1 From the Division of Endocrinology, Diabetes, Metabolism, and Nutrition (G.Y.G.,
minor criterion should be satisfied to differentiate this syn- 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.
drome from neuropathy associated with monoclonal
Data were presented in part at the Endocrine Society’s 86th Annual Meeting;
gammopathy of undetermined significance, myeloma, pri- New Orleans, La; June 16-10, 2004; and at the Endocrine Society’s 89th
mary systemic amyloidosis, and Waldenström disease. The Annual Meeting; Toronto, Ontario; June 2-5, 2007.
major criteria include polyneuropathy and a clonal plasma Individual reprints of this article are not available. Address correspondence to
proliferative disorder (almost always λ). The minor criteria Gunjan Y. Gandhi, MD, MSc, Division of Endocrinology, Diabetes, Metabo-
lism, and Nutrition, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-
include osteosclerotic bone lesions; Castleman disease; mail: gandhi.gunjan@mayo.edu).
papilledema; organomegaly, including lymphadenopathy; © 2007 Mayo Foundation for Medical Education and Research
836 Mayo Clin Proc. • July 2007;82(7):836-842 • www.mayoclinicproceedings.com
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.ENDOCRINOPATHY IN POEMS SYNDROME
structurally normal and without defining characteristics.15 TABLE 1. Criteria for Diagnosis of POEMS Syndrome2*
Therefore, it seems likely that the endocrine abnormalities Criteria type Description
reflect a functional rather than structural disturbance of Major Polyneuropathy
gland function. Monoclonal plasma proliferative disorder
Most of the information regarding endocrinopathies in Minor Sclerotic bone lesions†
POEMS syndrome is from isolated case reports or small Castleman disease†
Organomegaly (splenomegaly, hepatomegaly, or
case series that have not systematically studied the various lymphadenopathy
endocrine manifestations in this disorder. To take advan- Edema (pleural effusion or ascites)
tage of our institution’s experience with a large series Endocrinopathy (adrenal, thyroid,‡ pituitary,
gonadal, parathyroid, pancreatic‡)
of patients, we sought to determine the prevalence and Skin changes (hyperpigmentation, hypertrichosis,
characteristics of endocrinopathies at diagnosis of POEMS plethora, hemangiomata, white nails)
syndrome to further our understanding of this enigmatic Papilledema
disorder. Known Clubbing
associations Weight loss
Thrombocytosis
Polycythemia
PATIENTS AND METHODS Hyperhidrosis
All patients with POEMS syndrome who met minimal Possible Pulmonary hypertension
associations Restrictive lung disease
criteria for inclusion in the study were identified through Thrombotic diatheses
the Mayo Clinic dysproteinemia database.2 From January Arthralgias
1, 1960, through June 30, 2006, 170 patients (115 previ- Cardiomyopathy (systolic dysfunction)
Fever
ously described2,16) met both major criteria and 1 minor Low vitamin B12 values
criterion for the diagnosis of POEMS syndrome (Table 1). Diarrhea
Because of the high prevalence of diabetes mellitus and *Two major criteria and at least 1 minor criterion are required for diagno-
thyroid abnormalities, these diagnoses alone were not suf- sis. POEMS = polyneuropathy, organomegaly, endocrinopathy, M pro-
ficient to meet the minor criterion. Using a standardized tein, skin changes.
†Osteosclerotic disease or Castleman disease is usually present.
data extraction form, we abstracted information from the ‡Because of the high prevalence of diabetes mellitus and thyroid abnormali-
medical records of these patients regarding their endocrine ties, these diagnoses alone are not sufficient to meet this minor criterion.
abnormalities at the time of diagnosis of POEMS syn- From Blood,2 with permission.
drome. Diabetes mellitus and hypothyroidism were not
attributed to POEMS syndrome unless these reportedly nized endocrinopathy (median age, 50 years; interquartile
occurred months to years after the onset of at least another range, 43-59 years; 38 men).
feature of POEMS syndrome.
As we conducted our investigation, we noticed a dif- GONADAL AXIS
ference in the extent of endocrine evaluation over time. Hypogonadism was the most common endocrine abnor-
Patients seen before 2000 had few endocrine tests, particu- mality. Thirty-three (87%) of 38 men had testosterone
larly when they had no endocrine-related symptoms. Con- levels measured; 26 (79%) had levels below the lower limit
versely, patients seen in 2000 or later had a more complete of the normal range for total testosterone. Twenty-five
endocrine evaluation. Thus, we decided to focus our results (96%) of these 26 patients had estimation of free testoster-
on the subset of patients seen in 2000 or later. The Mayo one levels performed as well, which showed low levels in
Foundation Institutional Review Board approved the study all cases. Twenty-three (61%) of 38 men reported erectile
in accordance with Minnesota state law that regulates re- dysfunction. In 23 men with available data, 7 (30%) had
search from medical records. evidence of primary hypogonadism, whereas 16 (70%) had
secondary hypogonadism. Ten men (43%) had gynecomas-
tia, of whom only 1 had elevated estrogen levels (of the 4
RESULTS
men in whom estrogen levels were measured).
Of the 170 patients with POEMS syndrome, 106 were
treated before 2000, and 64 were treated in 2000 or later PROLACTIN AXIS
(Table 2). A total of 118 patients (69%; 95% confidence Among the 35 patients with measured prolactin levels, 10
interval, 62%-76%) had a recognized endocrinopathy (89 (29%; 7 men and 3 women) had levels higher than the upper
men; median age, 54 years, interquartile range, 47-63 limit of the normal range. In most cases, prolactin concentra-
years). Fifty-four (84%) of the 64 patients treated in 2000 tions were noted to be mildly elevated. Two women had
or later (95% confidence interval, 73%-92%) had a recog- irregular menses, 1 of whom also had galactorrhea.
Mayo Clin Proc. • July 2007;82(7):836-842 • www.mayoclinicproceedings.com 837
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.ENDOCRINOPATHY IN POEMS SYNDROME
TABLE 2. Endocrine Abnormalities in the Recent Cohort low albumin, 14 (27%) of 51 patients had true hypocalce-
(2000-2006)*†
mia. Parathyroid gland dysfunction was not routinely
No. (%) of patients determined. Of those with low calcium levels, 2 of 6 pa-
Characteristic (N=64)
tients tested had high parathyroid hormone (PTH) levels
Patients with endocrinopathy 54 (84) suggestive of secondary hyperparathyroidism. Two pa-
M/F 38/16
Median age (y) (IQR) 50 (43-59) tients with measured calcium levels had hypercalcemia,
Race neither of whom had PTH levels measured. Phosphorus
White 48 levels were elevated in 12 (36%) of 33 patients. One of
Hispanic 5
African American 1 the 64 patients had a low PTH level with a normal calcium
Mean body mass index (SD) 25 (4) concentration.
Erectile dysfunction 23/38 (61)
Hypogonadism (men) 26/33 (79)
Gynecomastia (men) 10/38 (26) MULTIPLE AXES
Hyperprolactinemia 10/35 (29) Twenty-nine (54%) of 54 patients had evidence of multiple
Hypothyroidism 28/48 (58) endocrinopathies in the 4 major endocrine axes (gonadal,
Glucose intolerance 24/50 (48)
Adrenal insufficiency 6/9 (67) thyroid, glucose, and adrenal).
Hypocalcemia 14/51 (27)
Evidence of multiple endocrine abnormalities 29/54 (54)
DISCUSSION
*Data are number (percentage) of patients unless otherwise indicated.
IQR = interquartile range. KEY FINDINGS
†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; Our series of patients with POEMS syndrome, to our
fasting glucose, 70 to 100 mg/dL; calcium, 8.9 to 10.1 mg/dL; phospho- knowledge the largest reported in the literature, confirms
rus, 2.5 to 4.5 mg/dL; morning cortisol, 7 to 25 µg/dL; adrenocorticotro- that endocrinopathy is a central feature of this disorder.
pic 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 Hypogonadism in men is the most common endocrine ab-
to 30 ng/mL for females. normality, whereas hypothyroidism and abnormalities of
glucose metabolism were frequently noted at the time of
THYROID AXIS diagnosis of POEMS syndrome. Of interest is the isolated
Elevated thyrotropin concentrations were noted in 28 elevation of ACTH levels noted in these patients (pre-
(58%) of 48 patients (17 men and 11 women). Half of these sumed to be responsible for skin hyperpigmentation, but a
patients (14/28) had mild increases in thyrotropin levels clear correlation could not be established from these data).
(>5 butENDOCRINOPATHY IN POEMS SYNDROME
TABLE 3. Clinical Characteristics of Our Study Patients Compared With 2 Previous Series*
Recent cohort
(2000-2006) Nakanishi et al3 Soubrier et al12
Characteristic (N=64) (N=102) (N=25)
Patients with endocrinopathy 54 (84) NR NR
M/F 38/16 69/33 17/8
Median or mean age (y) (IQR) 50 (median) (43-59) 46 (mean) 51 (mean)
Race NR
White 48
Hispanic 5
African American 1
Japanese 102
Erectile dysfunction 23/38 39/50 13/13
Gynecomastia 10/38 (men only) 43/63 10/13
Hyperprolactinemia 10/35 NR 4/17
Hypothyroidism 28/48 NR 10/22
Glucose intolerance 24/50 26/93 9/22
Adrenal insufficiency 6/9 NR NR
Evidence of multiple endocrine abnormalities 29/54 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 agents might have a role in the treatment of the endocrine
The cause of POEMS syndrome is unknown. Although the manifestations of POEMS syndrome.11 Interestingly, pro-
high prevalence of λ light chains (>95% of cases) is sug- lactin levels were elevated in several of our patients. Thus,
gestive of a key role in the pathogenesis, histopathologic VEGF could potentially account for organomegaly, skin
review of affected organs and nerves does not support that lesions, edema, and possibly polyneuropathy and endo-
it is a form of deposition disorder.3,17 Antibodies to human crinopathies in POEMS syndrome.
herpesvirus were reported in 78% of patients who have Many of the endocrine abnormalities seen in patients
POEMS syndrome with Castleman disease and 22% of with POEMS syndrome could be due to chronic illness or
those with POEMS syndrome without Castleman disease.18 illnesses commonly observed in this age population. Un-
No circulating antibodies against hormones or hormone fortunately, no studies have assessed endocrinopathies in
receptors seem to be present.1,12 No characteristic findings patients with POEMS syndrome compared with an age-
are seen in endocrine organ studies at autopsy.15 and sex-matched population or patients with chronic dis-
Considerable interest has been demonstrated in the role ease. Although previous studies have compared cytokines5
of cytokines (chiefly interleukin 1β, interleukin 6, and and VEGF8 levels in patients with POEMS syndrome to
tumor necrosis factor α) as mediators of POEMS syn- other causes of polyneuropathy (multiple myeloma, chron-
drome.5,19 The site of activation of the cytokine network is ic inflammatory demyelinating polyneuropathy), they did
not yet known, but macrophages, not T cells, are assumed not specifically report on endocrine laboratory or clinical
to be activated. Compared with patients with multiple my- abnormalities. As indicated in Table 4, the prevalence of
eloma, patients with POEMS syndrome had higher serum hypogonadism, diabetes, and hypothyroidism is signifi-
levels of proinflammatory cytokines (interleukin 1β, tumor cantly greater in patients with POEMS syndrome com-
necrosis factor α, and interleukin 6) and lower levels of an pared with population-based longitudinal cohorts.20-22
antagonistic cytokine (transforming growth factor β1),
suggesting a loss of balance between proinflammatory and HYPOGONADISM
anti-inflammatory cytokines.5 Vascular endothelial growth We confirmed the high prevalence of hypogonadism in
factor is the leading candidate as a pathogenic factor in patients with POEMS syndrome.2,3,12 Hypogonadism was
POEMS syndrome and often decreases with successful secondary (hypogonadotropic hypogonadism) in most
treatment.8-10 Also, VEGF plays a critical role in angiogen- cases. In comparison, Soubrier et al12 reported an equal
esis.11 One might hypothesize that overexpression of incidence of primary (hypergonadotropic hypogonadism)
VEGF in POEMS syndrome might affect several of the (5/9) and secondary (4/9) hypogonadism in these patients.
endocrine axes because of a disruption of the local balance In our series, a significant proportion of men who did not
of angiogenic factors that appears to be important in the report erectile dysfunction had low testosterone levels. We
regulation of hormone secretion in many endocrine glands. also noted gynecomastia in men and irregular menses in
Because dopamine agonists disrupt VEGF signaling, these women, which others have described.1,3,12
Mayo Clin Proc. • July 2007;82(7):836-842 • www.mayoclinicproceedings.com 839
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.ENDOCRINOPATHY IN POEMS SYNDROME
TABLE 4. Prevalence of Common Endocrine Disorders in the General Population
Compared With POEMS Syndrome20-22*
Prevalence (%)
General population
Patients with
Endocrine disorder Overall Men Women POEMS syndrome
Hypogonadism 12 (50-59 y) 79
Diabetes (diagnosed) 6.6 (40-59 y) 7.5 (40-59 y) 5.7 (40-59 y) 16
Impaired fasting glucose 29.9 37.2 22.9 32
Hypothyroidism
(clinical plus subclinical) 4.6 58
*POEMS = polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes.
Although estrogen was not routinely checked in our quency of impaired fasting glucose levels and diabetes
patients, other investigators have proposed hyperestro- mellitus in the general population, the number of patients
genemia as a unifying hypothesis for endocrinopathy.23 In with POEMS syndrome taking corticosteroids at diagnosis,
those patients, an accelerated conversion of androgens into and stress hyperglycemia from severe illness. We estab-
estrogens was found. Increased estrogen could potentially lished a clear temporal relationship between glucose intol-
also cause hyperprolactinemia either directly or by modify- erance and POEMS syndrome and ruled out corticosteroid
ing the estrogen-testosterone ratio.24 use at the time of testing in our series of patients.
The cause of hyperprolactinemia remains unclear. An
increased intracranial pressure in patients with POEMS HYPOTHYROIDISM
syndrome may result in disturbed hypothalamic function, After carefully establishing that at least 1 of the features of
loss of inhibitory dopaminergic pathways, and hyper- POEMS syndrome preceded hypothyroidism months to
prolacteinemia.1 Although hyperprolactinemia may cause years after the onset of hypothyroidism, we noted that a
hypogonadism, normalization of prolactin with bromo- significant proportion of patients had hypothyroidism.
criptine had no effect on androgen and gonadotropin lev- Most patients had mild primary hypothyroidism, which
els.1 Treatment of hypothyroidism when present did not is consistent with other reports.1,2,12,13,26,27 Interestingly,
resolve the hyperprolactinemia. Also, 2 eugonadal men Soubrier et al described secondary (central) hypothyroid-
with POEMS syndrome were noted to have primary fol- ism in 2 of 10 patients with hypothyroidism in their series
licle-stimulating hormone (FSH) hypersecretion, suggest- of 25 patients. Although the cause remains elusive, specific
ing that primary FSH hypersecretion in the absence of antibody-binding activity directed against pituitary tissue
primary testicular failure should be added to the list of was demonstrated in a patient with POEMS syndrome and
endocrinopathies of POEMS syndrome.25 An isolated el- hypothyroidism.28 However, the thyrotropin levels were
evation of FSH levels with normal levels of FSH and high. Thyroid microsomal antibodies or thyroglobulin anti-
testosterone can also occur in Sertoli cell–only syndrome, bodies have not been found.1
which has a wide variety of causes, including antineoplas-
tic therapy with radiation and chemotherapy. It is not ADRENAL INSUFFICIENCY
routine practice at our institution to obtain fertility data, Adrenal insufficiency has been described infrequently in
perform sperm analyses, or consider cryopreservation patients with POEMS syndrome.2,14,26 We noted an abnor-
of sperm before chemotherapy or radiotherapy in these mal ACTH stimulation test result in most of those tested.
patients. However, data are insufficient to comment on whether this
was primary or secondary adrenal insufficiency. Previous
GLUCOSE ABNORMALITIES case reports describing adrenal insufficiency in this disor-
An abnormality in glucose metabolism was a common der have noted it to be a primary adrenal disorder,14,26 but
endocrine manifestation in our series, a finding that is none measured adrenal autoantibodies. Bardwick et al1 did
consistent with previously reported large series.2,3,12 Most not detect circulating inhibitors of ACTH in the serum of
patients have impaired fasting glucose levels and need the 2 patients described. The isolated elevation in ACTH
lifestyle interventions. Patients with diabetes tend to have levels with a normal cortisol level (seen in 7 of 13 patients)
modest insulin requirements.1 Antibodies to pancreatic is- could indicate “compensated” cortisol levels; the fact that
let cells were not demonstrated in 2 patients with POEMS we saw this in more than half the patients tested (7/13)
syndrome.1 Potential confounders to the high incidence of indicates that this is unlikely to be attributable to assay or
glucose abnormalities to remember are the increased fre- biological variability.
840 Mayo Clin Proc. • July 2007;82(7):836-842 • www.mayoclinicproceedings.com
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.ENDOCRINOPATHY IN POEMS SYNDROME
CALCIUM ABNORMALITIES TABLE 5. Suggested Endocrine Review of Systems and
Laboratory Tests During Initial Evaluation of POEMS Syndrome*
Although experts have not associated calcium abnormali-
ties to POEMS syndrome, we noted that approximately Endocrine
axis Review of systems Initial laboratory tests
one third of patients in our series had low calcium levels.
Although parathyroid function was not routinely measured Thyroid Change in energy level Thyrotropin, free thyroxine
Skin and hair changes
in these patients, no evidence was available of primary Menstrual irregularities
hypoparathyroidism in those cases in which PTH levels Heat or cold intolerance
were measured. To our knowledge, there has been only 1 Change in bowel habits
Weight change
report of established primary hypoparathyroidism (low Mood changes
calcium, high phosphate, and undetectable PTH levels) Glucose Polyuria Fasting glucose (early
in association with vitamin D deficiency.13 Another case metabolism Polydipsia morning)
report described a patient with hypocalcemia, hyperphos- Polyphagia
Weight change
phatemia, low-normal vitamin D levels, and an inappropri-
Gonadal Change in libido Total and bioavailable
ately normal PTH level, suggestive of an abnormal para- Erectile dysfunction testosterone (early
thyroid response.26 Routine measurement of calcium and Menstrual irregularities morning), FSH, luteinizing
phosphate levels and, if abnormal, measurement of PTH, hormone, estradiol (in
women)
creatinine, and vitamin D levels may be prudent. Interest-
Prolactin Gynecomastia Prolactin (early morning)
ingly, Nakanishi et al3 reported hypercalcemia in 7 of 23 Galactorrhea
patients, although it is unclear if this was accurate because Breast engorgement
none had a serum calcium level greater than 10 mg/dL. The Menstrual irregularities
Headaches
elevated phosphate levels in our patients suggest impaired Visual changes
renal function or increased bone loss of calcium and phos- Adrenal Weight change Cortisol, ACTH (early
phate as possible mechanisms. Change in energy level morning)
Skin color changes
Salt craving
STUDY LIMITATIONS Muscle aches
Overall, the prevalence of endocrinopathy in our series is Calcium Paresthesias Calcium
likely an underestimate because most patients, especially regulation Muscle cramps
those seen before the turn of the century, had incomplete *ACTH = adrenocorticotropic hormone; FSH = follicle-stimulating hor-
endocrine evaluations. To enable us to gain a better under- mone; POEMS = polyneuropathy, organomegaly, endocrinopathy, M
standing of asymptomatic endocrine laboratory changes protein, skin changes.
seen early in the disease, we separately studied and de-
scribe patients seen in the last 6 years, who appear to be cian following up these patients over time, especially after
better characterized. This was a retrospective medical treatment.
record review with all its inherent biases. Thus, no stan-
dardized means were available for ensuring when and what SUGGESTED APPROACH TO EVALUATING ENDOCRINOPATHIES IN
laboratory tests were performed and if they were necessar- POEMS SYNDROME
ily repeated to confirm an abnormal test result. Cortisol, We suggest that all patients with POEMS syndrome have a
testosterone, glucose, and prolactin samples were in most thorough and systematic endocrine evaluation at diagnosis
cases obtained in the early morning. Because this is an of this syndrome. Clinicians should complete an endocrine
extremely rare disorder, a retrospective review has been the review of systems during the initial evaluation and obtain
preferred method of study until now. Most of the patients total and bioavailable testosterone, prolactin, fasting glu-
seen at our institution were white. This is an extension of cose, cortisol and ACTH specimens (all early morning) and
the first large North American patient population reported,2 thyrotropin and calcium specimens (Table 5). An endocri-
but with an emphasis on endocrine findings. We have no nologist should see patients with concerns or abnormal
follow-up information regarding progression of endo- levels for further assessment and treatment.
crine abnormalities or new development of endocrine dis-
orders. However, in the future, we plan to develop a sys- FUTURE DIRECTIONS
tematic method to track and obtain follow-up information To gain a better understanding of the pathogenesis of endo-
on these patients. Although we believe that this report is crinopathies in POEMS syndrome, researchers should fo-
helpful in guiding the evaluation today, future knowledge cus on studies that assess the role of cytokines and VEGF,
about the natural history of endocrinopathies in POEMS especially related to endocrine dysfunction. Whether endo-
syndrome may be particularly helpful to the frontline clini- crine disorders associated with POEMS syndrome improve
Mayo Clin Proc. • July 2007;82(7):836-842 • www.mayoclinicproceedings.com 841
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.ENDOCRINOPATHY IN POEMS SYNDROME
after successful treatment of the disease is unknown. Fol- 11. Goth MI, Hubina E, Raptis S, Nagy GM, Toth BE. Physiological and
pathological angiogenesis in the endocrine system. Microsc Res Tech. 2003;
low-up studies to better understand the evolution of endo- 60:98-106.
crine disorders in these patients are needed. 12. Soubrier MJ, Dubost JJ, Sauvezie BJ, French Study Group on POEMS
Syndrome. POEMS syndrome: a study of 25 cases and a review of the litera-
ture. Am J Med. 1994;97:543-553.
13. Cabezas-Agricola JM, Lado-Abeal JJ, Otero-Anton E, Sanchez-Leira J,
CONCLUSION Cabezas-Cerrato J. Hypoparathyroidism in POEMS syndrome. Lancet. 1996;
347:701-702.
The high prevalence of endocrinopathies in our study, to 14. Mauvais-Jarvis F, Bertherat J, Ravaud H, Thomopoulos P, Luton JP.
our knowledge the largest published series of POEMS POEMS syndrome with primary adrenocortical insufficiency [in French].
Presse Med. 1998;27:15-17.
cases, calls for a thorough endocrine investigation in pa- 15. Gherardi R, Baudrimont M, Kujas M, et al. Pathological findings in three
tients who present with this syndrome and vigilance in non-Japanese patients with the POEMS syndrome. Virchows Arch A Pathol
monitoring for treatable hormonal disorders that may Anat Histopathol. 1988;413:357-365.
16. Dispenzieri A, Moreno-Aspitia A, Suarez GA, et al. Peripheral blood
emerge during the disease. stem cell transplantation in 16 patients with POEMS syndrome, and a review of
the literature. Blood. 2004 Nov 15;104:3400-3407. Epub 2004 Jul 27.
17. Bergouignan FX, Massonnat R, Vital C, et al. Uncompacted lamellae in
We are grateful to Rebecca Bahn, MD, for contributing to our three patients with POEMS syndrome. Eur Neurol. 1987;27:173-181.
reporting of the potential association between VEGF over- 18. Belec L, Authier FJ, Mohamed AS, Soubrier M, Gherardi RK. Antibod-
expression and endocrine manifestations in patients with POEMS ies to human herpesvirus 8 in POEMS (polyneuropathy, organomegaly, endo-
syndrome. crinopathy, M protein, skin changes) syndrome with multicentric Castleman’s
disease. Clin Infect Dis. 1999;28:678-679.
19. Gherardi RK, Belec L, Fromont G, et al. Elevated levels of interleukin-
1β (IL-1β) and IL-6 in serum and increased production of IL-1β mRNA in
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