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Journal of Postgraduate Medicine
Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India
ISSN: 0022-3859 EISSN: 0972-2823
Vol. 52, Num. 2, 2006, pp. 145-147
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Journal of Postgraduate Medicine, Vol. 52, No. 2, April-June, 2006, pp. 145-147
Grand Round Case
A mentally challenged adult with tonic convulsions, dysmorphic face and sebopsoriasis
John Mathew, Sudeep K, Thomas N, Thomas M*
Department of Endocrinology and *Neurological Sciences, Christian Medical College, Ida Scudder Road, Vellore - 632 004, Tamil Nadu
Correspondence Address:Department of Endocrinology, Christian Medical
College, Ida Scudder Road, Vellore - 632 004, Tamil Nadu, drmathewjohn@yahoo.com
Code Number: jp06046
A 21-year-old man presented with increased frequency of intermittent tonic spasms of 3 weeks′ duration. There was also history of fever and extensive cutaneous lesions involving the body, scalp and nails of 6 weeks′ duration. From the age of 17 years, he experienced spontaneous paroxysmal tonic spasms involving extremities and trunk with retained consciousness and was on treatment with Carbamazepine and Sodium valproate. Behavioral problems were treated with Chlorpromazine, Nitrazepam and Trihexyphenidyl. For a week prior to admission, he was on treatment with Cefotaxime and Gentamicin for the febrile episode. He was born of a non-consanguineous union. Birth history and family history were non-contributory. Motor and mental milestones were delayed and he attended a school for the mentally challenged.
On examination, he was of normal stature (25th percentile), febrile
and delirious. He had myoclonic movements of both upper limbs with tonic
posturing of fingers. He had a dysmorphic face with low set ears, hyperteliorism,
narrow palpabral fissures and a broad forehead. The uvula was normal.
There was no limb weakness. Ocular examination showed early posterior
subcapsular cataract and papilledema. Well-defined scaly plaques with
peripheral erythema with fissuring over the forearm, neck, face, scalp,
groin and legs with palm and sole involvement, suggestive of sebospsoriasis
were present. He also had sub-ungual hyperkeratosis with distal discoloration
of the nails. Pubertal status was appropriate for age. On clinical assessment,
he was judged to have moderate mental retardation. On formal IQ testing,
his intelligence quotient (IQ) was 60 (Binet Kamat scale for intelligence)
Biochemical investigations and blood cultures were ordered and an urgent
CT scan of the brain [Figure - 1] was performed, which was followed by
a lumbar puncture.
What is the differential diagnosis for this presentation?
This patient had paroxysmal episodes of spontaneous tonic spasms involving
the limbs and extremities without loss of consciousness: paroxysmal non-kinesigenic
dyskinesia (PNKD). PKND can be familial (with an autosomal dominant inheritance)
in nature. The secondary causes of PNKD include multiple sclerosis, perinatal
hypoxia encephalitis, cystinuria, hypoparathyroidism, pseudohypoparathyroidism,
Wilson′s disease, thyrotoxicosis, head injury, hypoglycaemia, basal ganglia calcification, acquired immune deficiency syndrome (AIDS), diabetes mellitus, meningioma, cerebro-vascular accidents and Leigh syndrome. In view of fever with associated central nervous system symptoms, a lumbar puncture was also undertaken.
The non-enhanced CT scan showed bilateral basal ganglia calcifications.
The ventricular systems and basal cisterns were prominent and reflected
the degree of cerebral atrophy.
Name the conditions that would be included in the differential diagnosis
in the light of CT scan findings.
The various causes for bilateral basal ganglia calcification are given
in [Table - 1].[1]
The results of biochemical investigations were as follows: venous plasma
glucose: 106 mg/dl (80-120), Serum calcium: 3.3 mg/dl (8.5-10.5), Serum
Phosphorus: 8.8 mg/dl (2.5-4.5), Serum albumin: 3.4 mg/dl (3.5-5), Serum
magnesium: 1.32 mg/dl (1.8-3.0), serum creatinine: 0.9 mg/dl (0.8-1.2 mg/dl),
Testosterone: 3.92 ng/ml (3-10), FSH: 3.12 IU/L (1.4-9.6), Cortisol: 18.8
mcg/dl (>18), PTH: 8 pg/ml (10-65), TSH: 1.14 mIU/ml (0.5-4.5), FT4: 1.88
ng/dl (0.8-2.0), Sodium: 143 meq/l (135-145), Potassium: 4.3 meq/l (3.5-5),
Bicarbonate: 23 meq/l (22-29), Chloride: 94 meq/L (98-106), 25-OH Vitamin
D: 7.9 ng/ml.(10-40) Cerebrospinal fluid: Cells: 2 lymphocytes/mm3 (0-5
cells/mm3), Glucose: 93 mg/dl, Protein: 17 g/dl, Measles IgG Antibody:
negative. Brainstem Auditory Evoked Response: normal. 2D Echocardiogram:
normal. Karyotype: XY. Blood cultures showed significant growth of Enterococci.
Ultrasound study of the abdomen including the kidneys was normal.
What do these biochemical investigations indicate?
The investigations demonstrate the presence of hypocalcaemia, hyperphosphatemia
and low PTH levels. This is suggestive of hypoparathyroidism. The other
abnormal investigations in this group are hypomagnesaemia and low 25 hydroxy-vitamin
D levels. The low vitamin D levels are likely to be due to the homebound
state of the patient and chronic use of anticonvulsants. Low 25- hydroxy
Vitamin D levels can sometimes cause a syndrome resembling pseudohypoparathyroidism.[2]
The possible causes of hypomagnesaemia in this patient are aminoglycoside
usage, magnesium loss through the weeping skin lesions, reduced dietary
intake and use of magnesium free intravenous fluids. Since, 25-30% of
magnesium is bound to albumin, hypo-albuminemic states may lead to spuriously
low magnesium values.[3] The
presence of intra-cerebral calcifications establishes the fact that hypocalcemia
is long-standing. The low chloride levels are likely to be related to increased
cutaneous loss of chloride.
The presence of dysmorphic facies and mental retardation is in favour
of a congenital onset of diseases. The various aetiologies of congenital
hypoparathyroidsm
in this setting are summarized in [Table - 2].[4]
How do you treat hypocalcaemia in this patient?
In the acute phase, calcium gluconate may be given intravenously.
This should be followed by an intravenous infusion of calcium at 0.5-2
mg/kg/hour. Simultaneously, oral replacement of calcium and vitamin D should
be started: 2-4 g of calcium carbonate and 0.25 to 0.5 mg of Calcitriol.
Alphacalcidiol can also be used instead of Calcitriol. Hypomagnesaemia
should be considered in situations predisposing to the same. A low serum
magnesium level (< 1 mg/dl) indicates magnesium deficiency, but magnesium
deficiency can exist even with normal serum magnesium levels.[3] As
the serum calcium level has normalized, elevated serum phosphate concentrations
generally decline.[5]
The patient was treated with 10 ml of 10% calcium gluconate diluted in 10% dextrose given over 10 minutes, following which he was started on a calcium gluconate infusion. Two gram of 50% magnesium
sulfate (16.6 mEq) diluted in saline was given intravenously over 60 minutes.
This was gradually replaced with Calcitriol (0.5μg/day) and Calcium carbonate
(2 g/day). Magnesium replacement as an oxide salt was continued for two
weeks. The enterococcal septicaemia was treated with Ampicillin and Amikacin
for 10 days.
What are the neuropsychiatric manifestations of hypoparathyroidism?
Patients with hypoparathyroidism can present with parasthesias,
tetany, choreoathetosis, mutism, locked jaw, papilledema and generalized
tonic
clonic epilepsy.[6] They can
have gait disturbances, cognitive dysfunction, extrapyramidal signs,
muscle spasms, seizures and psychosis.[7] Myopathy,
senorineural deafness and idiopathic intracranial hypertension have been
described in hypoparathyroidism. Cerebellar signs and myelopathy due
to vertebral lamina overgrowth can be present in long standing disease.[8] A
reversible form of peripheral neuropathy that recovered following correction
of hypocalcemia has also been described in hypoparathyroidism.[9]
What are the skin manifestations of hypocalcaemia?
Psoriasis vulgaris, pustular psoriasis and impetigo herpetiformis
have been reported in hypoparathyroidism. Vitamin D and its analogues
appear to affect cell differentiation and cell proliferation and hypocalcaemia
may damage cell adhesion molecules such as cadherins, which depend on
calcium.[10] A
patient with generalized psoriasis associated with hypoparathyroidism
and HDR syndrome, cured by normalization of calcium has also been reported.[11] Patients
with autoimmune polyendocrinopathy syndromes can have associated mucocutaneous
candidiasis, alopecia and vitiligo as manifestations.
In patients with idiopathic hypoparathyroidism without other endocrine
autoimmunity, antibodies to calcium sensing receptor have been demonstrated
and a T cell mediated autoimmune destruction of the parathyroid glands
has been postulated. The study also showed an increased occurrence
of the HLADRB1FNx01 01 or DRB1FNx0109 alleles among the hypoparathyroid
patients.[12] The
fact that HLD -DR associations and T cell activation are major factors
that underlie the pathogenesis of psoriasis may be another reason for
the association between psoriasis and hypoparathyroidism.[13] Our
patient was treated with topical steroids with significant clearing
of the skin lesions within 2 weeks of therapy.
How will you monitor treatment in hypoparathyroidism?
The target of treating hypocalcaemia is to maintain calcium in
the low normal range (corrected calcium 8.0-8.5 mg/dl) and preventing
hypercalciuria
simultaneously at the same time. This is done by monitoring serum
calcium and urinary calcium (by either using a 24 hour urinary calcium
estimation
or calcium/creatinine ratio). Since there is an absence of the PTH
effect on conservation of renal calcium, there can be hypercalciuria
despite
having low normal serum calcium values.[5],[14] In
the event that a complication of hypercalciuria or hypercalcemia
develops, a reduction in the dose of calcium supplements and /or
calcitriol is
necessary. Annual ultrasound to screen for nephrocalcinosis should
be undertaken.
Ocular assessments should be undertaken yearly to assess the progress
of posterior subcapsular cataract.[14]
Our patient has chronic hypoparathyroidism of congenital origin with
dysmorphic features. This case highlights various issues in the management
of hypocalcaemia
and an interesting association with sebopsoriasis. The patient is
currently on follow up maintaining normal biochemical parameters
and free of
involuntary movements. There is no recurrence of sebopsoriasis after
correction of
hypocalcemia.
References
1. | Deepak S, Jayakumar B, Shanavas. Extensive Intracranial Calcification. J Assoc Physics India 2005;53:948. Back to cited text no. 1 |
2. | Shriraam M, Bhansali A, Velayutham P. Vitamin D deficiency masquerading as pseudohypoparathyroidism type 2. J Assoc Physics India 2003;51:619-20. Back to cited text no. 2 |
3. | Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med 2005;20:3-17. Back to cited text no. 3 [PUBMED] [FULLTEXT] |
4. | Singh J, Moghal N, Pearce SH, Cheetham T. The investigation of hypocalcaemia and rickets. Arch Dis Child 2003;88:403-7. Back to cited text no. 4 [PUBMED] [FULLTEXT] |
5. | Levine AM. Hypoparathyroidism and Pseudohypoparathyroidism In : Avioli LV, Krane SM (Editors) Metabolic Bone Disease and Clinically Related Diseases. 3rd ed. Academic Press: San Diego; 1998. p. 501-29. Back to cited text no. 5 |
6. | Idris MN, Sokrab TE. Unusual neuropsychiatric manifestations of hypoparathyroidism: report of two cases. East Afr Med J 1998;75:127-8. Back to cited text no. 6 [PUBMED] |
7. | Chiu JS, Wang YF, Chen CA, Lin SH, Lin YF, Chu P. Rocks in the head: extensive intracranial calcification. Intern Med J 2005;35:362-3. Back to cited text no. 7 [PUBMED] [FULLTEXT] |
8. | Jay CA, Abrams GM. Other endocrinopathies and the nervous system. In : Aminoff MJ (editor) Neurology and General Medicine. 3rd ed. Churchill Livingstone: Philadelphia; 2001. p. 383-96. Back to cited text no. 8 |
9. | Goswami R, Bhatia M, Goyal R, Kochupillai N. Reversible peripheral neuropathy in idiopathic hypoparathyroidism. Acta Neurol Scand 2002;105:128-31. Back to cited text no. 9 [PUBMED] [FULLTEXT] |
10. | Lee Y, Nam YH, Lee JH, Park JK, Seo YJ. Hypocalcaemia-induced pustular psoriasis-like skin eruption. Br J Dermatol 2005;152:591-3. Back to cited text no. 10 [PUBMED] [FULLTEXT] |
11. | Aksoylar S, Aydinok Y, Serdaroglu E, Coker M, Ozdemir F, Ozkinay F. HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome presenting with hypocalcemia-induced generalized psoriasis. J Pediatr Endocrinol Metab 2004;17:1031-4. Back to cited text no. 11 [PUBMED] |
12. | Goswami R, Brown EM, Kochupillai N, Gupta N, Rani R, Kifor O, et al . Prevalence of calcium sensing receptor autoantibodies in patients with sporadic idiopathic hypoparathyroidism. Eur J Endocrinol 2004;150:9-18. Back to cited text no. 12 |
13. | Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004;113:1664-75. Back to cited text no. 13 [PUBMED] [FULLTEXT] |
14. | Goltzman D, Cole DE. Hypoparathyroidism. In : Favus MJ (Editor) Primer on Metabolic Bone Disease and Disorders of Mineral Metabolism. 4th ed. Lippincott Williams & Wilkins: Philadelphia; 1999. p. 226-9. Back to cited text no. 14 |
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