Journal of Clinical and Translational Endocrinology: Case Reports 4 (2017) 5e7

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Journal of Clinical and Translational Endocrinology:

Case Reports
journal homepage: www.elsevier.com/locate/jecr

Case report of hypothyroidism presenting with myxedema ascites

Marc Atzenhoefer, MD a, *, Jeanette H. Man, BS b, Ehab R. Saad, MD, FACP, FASN c
a
Department of Medicine, Froedtert and Medical College of Wisconsin, USA
b
Medical College of Wisconsin School of Medicine, USA
c
Department of Nephrology, Froedtert and Medical College of Wisconsin, USA

a r t i c l e i n f o a b s t r a c t

Article history: Primary hypothyroidism rarely presents with ascites. This clinical finding in a patient with history
Received 29 December 2016 suggestive of hypothyroidism should prompt thyroid testing. Diagnostic workup should include a par-
Received in revised form acentesis and determination of the SAAG. Review of the literature revealed sixty three well documented
23 February 2017
cases of myxedema ascites. A majority of these had SAAGs of >1.1g/dL and total proteins of >2.5 g/dL.
Accepted 2 March 2017
Myxedema as a cause of ascites should be considered and ruled in by exclusion. Treatment with thyroid
replacement remains an effective solution with an excellent prognosis.
© 2017 The Author. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction
Ascites as a presenting symptom of primary hypothyroidism is
rare occurring in <1% of cases. An uncommon complication of hy-
pothyroidism, myxedema ascites is often diagnosed after lengthy
workups. Treatment with levothyroxine is a simple and inexpen-
sive solution that leads to complete resolution of true cases. This is
the first documented presentation of myxedema ascites in a solid
organ transplant recipient.
Case history
A 61 year old male presented with generalized weakness, dys-
pnea, and weight gain of 23 pounds over five months. Significant
medical history included end stage renal disease secondary to type
1 diabetes mellitus status post kidney-pancreas transplant in 1991
at age 36 as well as Non-Hodgkin's B-cell lymphoma treated with
rituximab monotherapy at age 43.
Physical examination was notable for anasarca, abdominal fluid
wave, and lower extremity pitting edema. Diagnostic workup
revealed an albumin of 2.6 g/dL, TSH of 186 uIU/mL, and free T4 of
0.1 ng/dL. Basic chemistry panel was notable for a creatinine of
1.9 mg/dL near the patient's historical baseline of 1.6 and blood urea
nitrogen of 53 mg/dL. Remaining electrolytes were within normal
* Corresponding author.
E-mail address: matzenhoefer@mcw.edu (M. Atzenhoefer).
limits (mmol/L): sodium 140, potassium 3.6, chloride 103, and bi-
carbonate 23. The electrocardiogram demonstrated low voltage
sinus bradycardia, a classic finding of profound hypothyroidism
(See Fig. 1).
Bilateral pleural effusions were also present on initial chest x-
ray and transthoracic echocardiogram was significant for global
hypokinesia without depressed ejection fraction also consistent
with profound hypothyroidism. Diagnostic paracentesis removed
60 ml of low protein fluid with a serum-ascites albumin gradient
(SAAG) of 1.5 g/dL.
Diuresis with intravenous albumin and furosemide was begun.
Given this patient's history of coronary artery disease, levothyrox-
ine was initiated at 25 mcg daily by mouth and titrated up to
50 mcg/day by discharge. His history of post-transplant lympho-
proliferative disease prompted computed tomography of the chest/
abdomen/pelvis (CT- CAP) which showed moderate ascites and a
benign peri-pancreatic cyst (See Fig. 2).
Complete abdominal ultrasound revealed normal liver
morphology and hemodynamics. Liver function tests were as fol-
lows: AST 47 u/L, ALT 28 u/L, alkaline phosphatase 50 u/L, amylase
233 u/L, and lipase of 90 u/L. Serology for HBV, HAV, and HCV were
negative. Serum ceruloplasmin, alpha-1-antitrypsin, anti-nuclear/
mitochondrial/smooth muscle antibodies, and serum protein/im-
munoglobulins returned within normal limits.
Aggressive diuretic regimen was de-escalated to his pre-
hospitalization maintenance dose of 40 mg/day early during the
hospital course. On day of discharge his pertinent medications
included oral levothyroxine 50 mcg/day and maintenance dose
furosemide 40 mg/day. Following one month of thyroid

http://dx.doi.org/10.1016/j.jecr.2017.03.001
2214-6245/© 2017 The Author. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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6 M. Atzenhoefer et al. / Journal of Clinical and Translational Endocrinology: Case Reports 4 (2017) 5e7

Fig. 1. Electrocardiogram.

Discussion

Ascites is an uncommon manifestation of hypothyroidism and

Fig. 2. Computed tomography of abdomen.
replacement therapy, improved constitutional symptoms mirrored
the clinical resolution of his ascites & pleural effusions (See Table 1).
rarely the primary presenting symptom. Review of the literature
revealed 64 documented cases. In 1950, Paddock described an as-
cites that could not be explained by decreased cardiac output,
increased capillary permeability, or protein accumulation which he
attributed to hypothyroidism [1]. This case adds data that further
clarifies the pathophysiology of myxedema.
Hyaluronic acid (HA) is a non-sulfated glycosaminoglycan that is
present throughout the body. This simple molecule influences
various cellular functions including motility, adhesion, prolifera-
tion, and suppression of differentiation [2]. HA degradation is
accomplished through the activity of three enzymes, most of which
are localized within liver endothelial cells [2]. Many factors have
been shown to influence the kinetics of HA elimination, however
urinary excretion plays a negligible role.
In hypothyroid patients, low levels of circulating thyroxine (T3)
result in decreased activity of various enzymes. Although normally
thought of as a stimulating molecule, T3 exerts an inhibitory effect
on HA synthesis. Human fibroblasts exposed to sub-physiologic

Table 1
Thyroid function test results.

Weeks from diagnosis 0 2 4 8 13 15 18

Thyroid Stimulating Hormone (ng/dL) 186 121.7 18.36 10.7 10.35 12.24 2.48
T4 Free (uIU/ml) 0.10 0.64 1.10 1.50 1.33 1.18
Thyroid Peroxidase Antibody (IU/ml) 8
Thyroglobulin Antibodies (IU/ml) <20

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 M. Atzenhoefer et al. / Journal of Clinical and Translational Endocrinology: Case Reports 4 (2017) 5e7
concentrations of T3 revealed a dose dependent increase in syn-
thesis of radiolabeled glycosaminoglycans [3].
It has been previously postulated that increased extravasation of
plasma proteins, specifically albumin, overwhelm lymphatic return
resulting in serous cavity effusions [4]. Other cases of myxedema
ascites often report total protein contents of >2.5 g/dL [4]. However,
increased albumin extravasation is not the cause of the fluid
accumulation as the SAAG is commonly >1.1 g/dL [4]. Other pro-
teins must be present to account for the elevated level in
myxedema ascites. This is the first time the HA component has
been analyzed.
Diagnostic paracentesis fluid yielded 190 ng/mL of HA which is
modestly elevated compared to that of cirrhotic patients which
range from 600 to 1600 ng/mL [5]. Oncotic draw by peritoneal al-
bumin or HA is unlikely the major driver of ascites accumulation as
previously thought. SAAGs of >1.1 g/dL suggest increased capillary
hydrostatic pressures which are absent in myxedema. We therefore
postulate that HA induces capillary leak resulting in transudative
fluid accumulation.
Multiple etiologies to our patient's anasarca and serous effu-
sions were considered. No significant proteinuria was present to
suggest a renal contribution to his presenting complaints. Dipstick
urinalyses were negative for protein 2 months prior, 1 month prior,
as well as on admission. Portal hydrostatic pressures were normal
on complete abdominal ultrasound which ruled out cirrhosis, he-
patic/portal vein obstruction, and cardiac congestion. Mild hypo-
albuminemia was noted to have preceded clinical presentation and
endured beyond resolution of ascites. Given his outpatient diuretic
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7
dose remained unchanged, hypoalbuminemia due to malnutrition
or synthetic liver dysfunction was a less likely contributor. Other
unusual causes of his presentation including malignant, traumatic,
and pancreatic ascites were considered and not evident on CT-CAP.
Deranged amylase and lipase were at baseline for this patient status
post pancreas transplant with urinary drainage. Profound hypo-
thyroidism presenting with myxedema ascites was our ultimate
diagnosis after complete symptom resolution on levothyroxine
150 mcg/day.
This case demonstrates the importance of maintaining a broad
differential when approaching ascites of uncertain etiology. Hy-
pothyroidism rarely presents with ascites but can be considered
after common causes have been ruled out. Diagnostic workup
should include a paracentesis with determination of the SAAG.
Treatment with thyroid hormone remains an effective therapy with
excellent prognosis.
References
[1] Paddock KF. Massive ascites due to myxedema - report of a case. N Engl J Med
1950 May;242:822e3.
[2] Stern R. Hyaluronan catabolism: a new metabolic pathway. Eur J Cell Biol 2004
Aug;83(7):317e25.
[3] Smith TJ, Murata Y, Horwitz A, Philipson L, Refetoff S. Regulation of glycos-
aminoglycan synthesis by thyroid hormone in vitro. J Clin Invest 1982
Nov;70(5):1066e73.
[4] Ji JS, Chae HS, Cho YS, Kim HK, Kim SS, Kim CW, et al. Myxedema ascites: case
report and literature review. J Korean Med Sci 2006 Aug;21(4):761e4.
[5] Lai KN, Szeto CC, Lam CW, Lai KB, Wong TY, Leung JC. Increased ascitic level of
hyaluronan in liver cirrhosis. J Lab Clin Med 1998 Apr;131(4):354e9.