BONFÁ, Eloisa

KAJITANI, Thayana Ribeiro

PEREIRA, Rosa M. R.

SILVA, Renata Viana da

PubMed

Universidade de São Paulo

Clinics

Hypoparathyroidism mimicking ankylosing spondylitis and myopathy: a case report

RCAAP - Repositório Científico de Acesso Aberto de Portugal

Kajitani, Thayana Ribeiro

Silva, Renata Viana da

Bonfá, Eloisa

Pereira, Rosa M. R.

USP Portal de Revistas (Univ. de São Paulo)

Biblioteca Digital da Produção Intelectual da Universidade de São Paulo (BDPI/USP)

CASE REPORT
Hypoparathyroidism mimicking ankylosing
spondylitis and myopathy: a case report
Thayana Ribeiro Kajitani, Renata Viana da Silva, Eloisa Bonfa´, Rosa M. R. Pereira
Rheumatology Division, Hospital das Clinicas da Faculdade de Medicina da Universidade de Sa˜o Paulo, Sa˜o Paulo/SP, Brazil.
Email: rosamariarp@yahoo.com
Tel.: 55 11 3061-7213
INTRODUCTION
Idiopathic hypoparathyroidism (HP) is an induced or
inherited condition characterized by insufficient secretion of
parathyroid hormone. The clinical manifestations of this
condition are varied, and pain and stiffness affecting the
back and hips resembling ankylosing spondylitis is an
under-recognized symptom in these patients. Here, we
report a case of delayed diagnosis of hypoparathyroidism
referred to a rheumatologist due to progressive inflamma-
tory back pain and myalgia.
Idiopathic hypoparathyroidism is an induced or inherited
condition of unknown etiology and is characterized by
insufficient secretion of parathyroid hormone due to
atrophy or absence of parathyroid glands, which leads to
hypocalcaemia and hyperphosphatemia.1
Hypoparathyroidism has multiple clinical manifesta-
tions, which primarily involve tissues of ectodermic
origin.2 Pain and stiffness affecting the back and hips,
limited movement and posture resembling that seen in
patients with ankylosing spondylitis is an under-recog-
nized feature in patients with this condition.1,3 Muscular
complaints by these patients are common because the
concentration of calcium ions is important for the main-
tenance and control of several biochemical processes
during muscle contraction. Hypocalcaemia causes hyper-
excitability of nerves and muscles, and a sporadic increase
in muscular enzymes.4
Here, we report a case of delayed diagnosis of hypopar-
athyroidism referred to a rheumatologist due to progressive
inflammatory back pain and myalgia with concomitant
elevation of inflammatory markers and muscle enzymes.
The patient was initially erroneously diagnosed with
ankylosing spondylitis (AS) and idiopathic myopathy.
This case reinforces the relevance of investigating the
underlying mineral metabolism disturbances in patients
with inflammatory diseases.
CASE REPORT
A 40-year-old man was referred to the Rheumatology
Outpatient Clinic with a fifteen-year history of progressive
inflammatory back and neck pain and prolonged (two
hours) morning stiffness. He also complained of diffuse
myalgia, muscle cramps, and frequent changes in bowel
habits characterized by chronic diarrhea (intermittent liquid
diarrhea without abdominal pain, mucous or blood, usually
occurring after meals). He reported a history of epilepsy
since three months of age and cataracts by age 31. He had no
history of surgical excision or damage to the parathyroid
gland, radiation or neoplastic/granulomatosis infiltration.
He also denied consanguinity, Arab ancestry, deafness or
recurrent oral candidiasis.
Upon physical examination, the patient displayed a
typical AS posture with decreased spinal mobility, a neck
rotation of 10 ,˚ chest expansion of 1.5 cm, and a Scho¨ber test
measurement of 10.5 cm. His hip movement was markedly
restricted in all directions, particularly flexion and rotation.
The Fabere test was positive. The patient fulfilled the
modified New York criteria for ankylosing spondylitis.5
Assessment of the patient’s muscle strength revealed Grade
IV reduction in all four limbs. Trousseau’s and Chvostek’s
signs also gave negative results. The patient had dental
abnormalities and a cognitive deficit (two years’ education
and a Mini-Mental State Examination score of eight), but
cleft palate, growth retardation, microcephaly, microphthal-
mia, and small hands and feet were not observed. Dental
abnormalities on a panoramic X-Ray revealed few erupted
teeth and the presence of multiple impacted teeth in the
maxilla and mandible, producing a change in anatomical
size and shape.
Laboratory investigation revealed hypocalcaemia (cal-
cium 4 mg/dL, ionized calcium 2.3 mg/dl), hyperpho-
sphatemia (5.3 mg/dl), undetectable parathyroid hormone
(,3 pg/ml) and vitamin D levels within the normal range
(56.1 ng/ml). Inflammatory markers (CRP 29.9 mg/dl and
ESR 31 mm) and muscle enzymes (CPK 2805 U/l, aldolase
8.6 U/l and lactic dehydrogenase 1397 U/l) were elevated
(Table 1). The patient did not express HLA-B27.
Tests for anti-nuclear antibodies and rheumatoid factor
were negative. The patient’s thyroid hormones, serum,
and urinary cortisol were normal. Blood counts and
glucose, urea and creatinine levels were also within
normal ranges. Serology for viral hepatitis, syphilis,
HIV, and HTLV were negative. Echocardiogram and renal
ultrasound were normal. A brain CT scan revealed
calcifications in the basal ganglia, thalamus, and cerebel-
lum. A mandibular panoramic radiograph confirmed
hypoplasia and dental malformations. Electromyography
was normal.
Bone fusions in the cervical spine, calcification of
ligaments and syndesmophytes in the lumbar spine were
observed through spine radiography (Figure 1), and Grade
Copyright  2011 CLINICS – This is an Open Access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-
commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.
CLINICS 2011;66(7):1287-1290 DOI:10.1590/S1807-59322011000700028
1287
II (right)/Grade III (left) sacroiliitis was observed through
sacroiliac joint radiography. Computed tomography (CT)
revealed ankylosis foci at the sacroiliac joint (SI) and
bilateral ossification of the iliolumbar ligament (Figure 2B).
Similarly, magnetic resonance imaging demonstrated ossi-
fication of the iliosacral ligaments in the lower portions of
the sacroiliac joints and no significant findings in the upper
portions of the SI joint (Figure 2C).
Bone mineral density evaluated by DXA revealed a Z-
score of +4.4 SD at the lumbar spine, -0.2 SD at the total
femur and -1.0 SD at the femoral neck.
Treatment with 2 g/day calcium carbonate and 1 mg
calcitriol led to evident clinical and laboratory improvement
including normalization of the bowel habits. Increasing the
calcium dose to 4 g/daywas recommended. At the following
visit, the patient had stopped taking the medicine, and the
laboratory parameters consequently worsened, particularly
inflammatory markers and muscle enzymes (Table 1). The
importance of treatment adherence was reinforced, and
calcium supplements were increased to 6 g/day, normal-
izing the serum calcium and muscle enzymes and reducing
inflammatory markers. Concomitant improvement of neck
and back pain, disappearance of the cramps and muscle pain
and normalization of bowel habits were observed.
DISCUSSION
To our knowledge, this is the first case report of idiopathic
HP simulating AS associated with idiopathic myopathy.
The diagnosis of HP was confirmed by hypocalcemia,
hyperphosphatemia, and undetectable PTH. The chronic
development of hypocalcemia may explain the absence of
tetany in this case. In fact, the most prominent symptoms of
tetany usually occur in acute forms of hypocalcemia and the
development of tetany symptoms depends on the duration,
severity, and rapidity of hypocalcemia.6
Developmental disorders are unlikely in this case be-
cause the patient did not exhibit the typical characteristics
of DiGeorge Syndrome/Catch-22,7 hypoparathyroidism-
sensorineural deafness-renal dysplasia syndrome,8 hypopa-
rathyroidism-retardation-dysmorphism or Kenny-Caffey
syndromes.9 Parathyroid gland destruction was excluded
given that the patient did not have a history of surgical
excision or radiation therapy. The patient had no family
history or clinical features suggestive of autoimmune poly-
endocrinopathy-candidiasis-ectodermal dystrophy.10 Auto-
immune adrenal involvement was also excluded as the serum
and urinary parameters were within normal ranges and
clinical symptomswere absent. In addition, the classic triad of
Kearn-Sayres syndrome (KSS) was not observed, and the
muscle complaints began late in life.11 Based on the above
evidence, the probable diagnosis is idiopathic HP, although
other rare defects cannot be excluded because specific genetic
analyses were not performed.
Table 1 - Laboratory data and treatment.
January
2010 February 2010
April
2010
May
2010 Reference values
Serum calcium, mg/dl 4 6.3 4.8 8.6 8.6 -10.2
Calcium ionic, mg/dl 2.3 3.5 2.4 4.6 4.6 – 5.3
Phosphorus, mg/dl 5.3 4 5.4 4.1 2.7 - 4.5
25 OH Vitamin D, ng/ml 56.1 NR 40.5 45.2 30 - 100
Parathormone, pg/ml ,3 NR ,3 16 - 87
C-reactive protein, mg/dl 29.9 14.4 27.2 18.5 ,5
Erythrosedimentation rate, mm 31 13 20 16 4.6 – 13.2
Aldolase, U/l 8.6 6.4 7.2 4.6 ,7.6
Creatine phosphokinase, U/l 2805 379 505 147 39 – 308
Lactate dehydrogenase, U/l 1397 640 797 460 240 – 480
Treatment None Calcium 2 g/day +
1 mcg/day calcitriol
Treatment
discontinuation
Calcium 6 g/day
+ 1 mcg/day calcitriol
Figure 1 - Lateral radiograph of lumbar spine showing marginal
syndesmophytes (arrows).
Hypoparathyroidism
Kajitani TR et al.
CLINICS 2011;66(7):1287-1290
1288
Occasionally, patients with HP may have clinical and
radiologic characteristics resembling AS1 due to paraver-
tebral calcification and ossification12. The syndesmophyte
in our HP patient, which exhibited the origination in the
vertebral margin and preservation of disc space character-
istic of AS, led to the misdiagnosis of AS. This finding is
distinct from osteoarthritis in which osteophytes are
horizontal and there is a significant reduction in disc
space.13 The predominant localization in the lumbar region
also suggested the diagnosis of AS, although any spinal
location may be involved in HP.13 Diffuse idiopathic
skeletal hyperostosis (DISH) was unlikely, considering the
radiologic spine features, the early appearance of calcifica-
tions (before the fourth decade) and the absence of co-
morbidities such as dyslipidemia and diabetes mellitus
type 2.12
The radiographic findings in the sacroiliac joint were
predominant in the lower portion with ossification of the
iliolumbar ligament, whereas the involvement is more
common in the upper region of the joint in AS. In addition,
the evident ossification at the hip joint with preserved joint
space is not characteristic of AS but has been reported in
HP.1 Moreover, the lack of HLA-B27 expression may reduce
the likelihood of the AS diagnosis as over 90% of AS
patients are positive for this allele,13 although no data
regarding the frequency of HLA-B27 in the healthy Brazilian
population are available.
Of note, the extensive basal ganglia calcification in our
case has been reported more often in HP patients with spine
involvement than in those without this complication,13
suggesting a disseminated process of calcification associated
with mineral metabolism disturbance. Reinforcing this
possibility, long-term HP disease was more often associated
with spinal involvement,13 which was also observed in the
patient evaluated herein. In addition, there is much in vitro
evidence that hyperphosphatemia may have a proinflam-
matory role14 that could ultimately contribute to the
calcification observed in our patient.
The novel description of concomitant association of HP
and spondyloarthritis with myopathy was supported by
the diminished muscle strength and marked muscle
enzyme elevations. Chronic hypocalcemic myopathy sec-
ondary to HP and raised serum CK concentration has
rarely been reported15 and is probably an under-recog-
nized condition due to the patient’s adaptation to long-
standing hypocalcemia. The most likely explanation of this
condition is that the increased permeability of the muscle
membrane induced by hypocalcemia leads to CK release.16
The inverse correlation between CK and serum calcium
concentrations as well as the normal electromyographic
findings observed in this case support this possibility. Of
note, rhabdomyolysis was excluded due to normal urine
analysis, the absence of acute renal failure and the positive
response to calcium treatment.
Idiopathic HP has been described as an unusual cause of
diarrhea17 as observed in the present case. Reinforcing this
possibility, the bowel habits were normalized after hypo-
calcemia correction.
Figure 2 - A- Hip radiograph showing bilateral ossification at the superior acetabular margin (arrows). B- Pelvis CT showing foci of
ankylosis in the lower portion of the sacroiliac joint (arrows). C- Axial fat sat T2-weighted turbo spin-echo showing the lower portion of
the sacroiliac joint with ossification of the iliosacral ligaments (large arrows). There are no significant findings in the upper portions of
the sacroiliac joint (small arrows).
CLINICS 2011;66(7):1287-1290 Hypoparathyroidism
Kajitani TR et al.
1289
Importantly, the clinical and laboratory improvements
achieved solely with calcium and calcitriol supplementation
confirmed the diagnosis of HP and excluded the associa-
tions with ankylosing spondylitis and idiopathic myopathy,
as inflammatory rheumatic diseases are unresponsive to this
therapy.
This case emphasizes the importance of recognizing rheu-
matic manifestations of HP to preclude unnecessary treat-
ments. HP should be considered in the differential diagnosis of
spondyloarthropathies and myopathies, and calcium may be
included in the diagnostic workup of these patients.
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Hypoparathyroidism
Kajitani TR et al.
CLINICS 2011;66(7):1287-1290
1290


Thayana Ribeiro Kajitani

Renata Viana da Silva

Eloisa Bonfá

Rosa M R Pereira

Crossref

Comment on article by van der Linden et al. Evaluation of diagnostic criteria for ankylosing spondylitis: a proposal for modification of the New York criteria. Arthritis Rheum.

HDR syndrome: a novel ‘‘de novo’’ mutation in GATA3 gene.

High bone mass and hypocalcaemic myopathy in a patient with idiophatic hypoparathyroid. Clin Rheumatol.

Hypocalcemic induced increase in creatine kinase in rats. Pediatr Neurol.

Hypocalcemic myopathy without tetany due to idiopathic hypoparathyroidism: case report. Arq Neuropsiquiatr.

Hypocalcemic myopathy without tetany due to idiopathic hypoparathyroidism. Arq Neuropsiquiatr.

Hypoparathyroidism presenting as myopathy with raised creatine kinase.

Hypoparathyroidism simulating ankylosing spondylitis.

Idiopathic hypoparathyroidism mimicking diffuse idiopathic skeletal hyperostosis.

Impaired T(H)17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy-candidiasis- ectodermal dystrophy.

Late-onset idiopathic hypoparathyroidism as a cause of diarrhoea.

Presence of spondyloarthropathy and its clinical profile in patients with hypoparathyroidism. Clinical Endocrinology.

Reduction of hyperphosphatemia is related with the reduction of Creactive protein in dialysis patients. Study in sevelamer-resistant dialysis patients treated with chitosan chewing gum as salivary phosphate binder. Ren Fail.

Sanjad-Sakati syndrome/Kenny-Caffey sı ´ndrome type 1: a study of 21 cases in Kuwait.

Uncommon case of ankylosing spondylitis associated with spontaneous occurring hypoparathyroidism. Rheumatol Int.

Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2.2 deletion syndrome.

What is Kearns-Sayre syndrome after all? Arch Neurol.

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322011000700028

Hypoparathyroidism mimicking ankylosing spondylitis and myopathy: a case report

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