Ahmadi Patient identification A 35 yo woman single from and living in Shahriyar housewife Chief complain generalized musculoskeletal pain Present illness This is a 35 yo woman who was well until 7 month age that gradually developed bone ID: 932482
Download Presentation The PPT/PDF document "In the name of GOD Dr Noshin" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
In the name of GOD
Slide2Dr Noshin
Ahmadi
Slide3Patient identification
A 35 y/o woman ,single, from and living in
Shahriyar
, housewife
Chief complain: generalized musculoskeletal pain
Slide4Present illness
This is a 35 y/o woman who was well until 7 month age that gradually developed bone
and musculoskeletal pain. she developed claudication and was unable to do usual daily activity. she also suffered from proximal myopathy as she was not able to stand up from bench without help and raise her hand up to her head
She also mentioned
carpopedal
spasm and perioral
parestesia
1week before admission which was resolved after receiving calcium
gloconate
without laboratory evaluation.
In her summary file, decreased proximal muscular force especially in right lower limb(3/5) was mentioned , and she had positive trousseau sign
Slide5Previous laboratory
data(96/3-4)
Ca
=8.2 6.8 mg/dl
P=5.4
3.3 mg/dl
Na=138
mg/dl
Mg=2.4
mg/dlVit D=8 ng/dlAlb=4.4 g/dlEsr=65pTH =475 pg/mlAlkp =854 u/l
Slide6Previous laboratory data(96/3-4)
24hurine collection
volum
=1500
Cr=16.35 mg/24h/kg
ca
=109 mg/24h p=1020 mg/24hHypokalemia and metabolic alkalosis
Slide7Previous laboratory data
Wbc
=7160
Hb
=13.6 10.6
m
cv=85
Plt
=433000
Iron=45 tiBC=311 Ferittin=6 Urea=33 cr=0.7 tsh=5.2 t4=5.6Aldestrone=169(30-400)HLAB27=NEGPANCA=NEGCANCA=NEG
ANTI CCP=NEG
Slide8Previous laboratory data
ANA=NEG
ANTI ENDOMISYAL AB=NEG
ANTI TTG=NEG
HbsAg
=NEG
HCv
AB=NEG
HIV 1,2 AB=NEG
WRIGHT=NEG
Slide9Slide10Slide11Slide12Slide13Slide14Slide15Slide16Slide17Slide18Slide19Chest and abdomen pelvic
ct
Normal except a 3-4 mm nodule in upper right lung lobe
Slide20Bone densitometry
T score
Z score
L1-L4
-2.8
-2.8
TOTAL
-3
-2.9
Slide21ENDOSCOPY AND COLONOSCOPY
NORMAL
Slide22EMG -NCV
4 LIMBS- NORMAL
Slide23From pubic ramus
BIOPSY
Osteitis
fibrosa
cystica
Slide24Slide25Then she received calcium carbonate ,calciteriol , vitamin D, and POTASSIUM CHOLORIDE tab and referred to
T
aleghani
hospital for more evaluation
Slide26Past medical history
She has no history of illness
No cigarette smoking or alcohol use
Slide27Familly history
No family history of metabolic disease
Mother has
Htn
controlled with oral drugs
Slide28Review of system
Anorexia
Weigh loss about 10 Kg
One episode of hemoptysis during previous admission –not repetition
Spotting between regular menstruation
Slide29PHYSICAL EXAMINATION
Height=158
Weight=48
BMI=19.22
HR=84
BP=90-110/70-65
No fever
Heart sound=normal
Breast=normal
Lymphadenopathy= not detected lung =normal Abdomen pelvic=inguinal scar of biopsy Force 5/5No arthritis No limitation of joint movementGOVERN sign =positive
Slide30Thyroid sonography
Right :22 *12* 39
Left: 26*11*37
Isthnus:1.67mm
Multiple nodules in both sides ,largest in left :5.6*4.4mm, right side 5.3*4.5
Vascular flow is seen in both nodules
Slide31Breast sonography
Mild fibrocystic change in both sides no obvious mass or lymphadenopathy is seen
Axillary lymph node is not seen
Slide32Kidney sonography
Left kidney:123mm
Right kidney:122 mm
No stone , on
hydronephrosis
. No calcification
Slide33Slide34Slide35Slide36Laboratory data
96/7/1 96/7/3
Ph
=7.44
7.44 metabolic alkalosis
Pco2=57 47
Hco3=38 32
Pth
=140
pg/dl (475 179 140) high PTH25 hydroxy vit D=18 ng/dl (8 26 18) Low vitamin levelCa=8.3mg/dl 9.3 8.2Ph=4.4md/dl 3.7
Mg=2.4mg/dlESR=71 65K=2.6mg/dl 3 3.2 hypokalemiaCr=0.8(GFR=74)Uric acid=6.1
Na=137mg/dl
Alb
=4.4g/dl 3.8
Wbc
=8.7 /u
Rbc
=3.9
Hb
=10.9 g/dl
Mcv
=82
fl
Plt=547 *10*10*10Feritin=8Anti tpo=43 iu/ml
Slide38Problem list
Musculoskeletal pain
Hypocalcaemia
High PTH
Hypophosphatemia
Vitamin D deficiency
Hypokalemia
Metabolic alkalosis
10 Kg weight loss
High EsRIDA
Slide39Major causes
of
hypocalcaemia
with high PTH
vitamin D deficiency or resistance
Pth
resistance(missense mutation ,
pseodohypoparathyroidism
,
hypomagnesemia) Renal diseaseLoss of calcium from the circulationDrugsDisorders of magnesium metabolism
Slide40Slide41CELIAC
celiac disease now often presents later between the ages of 10 and 40.
Classic disease
The classic definition of celiac disease or gluten-sensitive
enteropathy
includes the following three features: villous atrophy; symptoms of
malabsorption
such as
steatorrhea,weight loss, or other signs of nutrient or vitamin deficiency ; and resolution of the mucosal lesions and symptoms upon withdrawal of gluten-containing foods, usual within a few weeks to months
Slide42Atypical celiac disease
Patients
with atypical disease exhibit only minor gastrointestinal complaints.
A number of
nongastrointestinal
manifestations of celiac disease have been described
. Metabolic
bone disease is common in celiac disease and can occur in patients without gastrointestinal symptoms. These patients have secondary hyperparathyroidism that is probably due to vitamin D deficiency
Osteomalacia
due to vitamin D deficiency that is also sometimes seen, although its exact prevalence is unknown
Slide43Celiac diagnosis
The serologic test (IgA-
tTG
) could be falsely negative. IgA or
IgG
gliadin
peptide antibody testing may be useful. However a small bowel biopsy is needed to make a diagnosis.
HLA typing for DQ2 (DQA1*05; DQB1*02) and DQ8 (DQA1*03; DQB1*0302) may be useful in individuals with equivocal small bowel histologic findings since celiac disease is unlikely if neither is
presentNon-celiac gluten sensitivity It remains unclear whether there is a category of patients with symptomatic response to gluten but without serologic evidence of celiac disease, termed nonceliac gluten sensitivity
Slide44Endocr Rev.
2001 Aug;22(4):477-501.
Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications.
Lips P
Slide45Slide46Loss of calcium from circulation
Hyperphosphatemia
Tumor
lysis
syndrome
Acute pancreatitis
Acute respiratory alkalosis
Acute sever illness
Osteoblastic metastasis
Slide47Osteoblastic metastases
,
with increased calcium uptake and
utilisation
: primarily carcinoma of the prostate or breast but also reported in gastrointestinal, lung
, thyroid
, salivary gland, and neuroendocrine cancer. In the rare
osteosclerotic
myeloma with or without POEMS syndrome, the same mechanism probably
underlieshypocalcaemia.
Slide48Turk J
Gastroenterol
.
2014 Dec;25
Suppl
1:284-6.
doi
: 10.5152/tjg.2014.4404.
Osteoblastic metastasis from signet ring cell gastric cancer in a young male.
Ermiş F1, Erkan ME, Besir FH, Oktay M, Kutlucan
A, Aydın Y.
This article
presented a rare case of signet ring cell gastric adenocarcinoma in early stage with
osteoblastic
metastasis
Slide49Postgrad Med.
2017 Mar;129(2):299-303..
Generalized high bone mineral density on bone density scanning: a case of gastric carcinoma with bone metastasis.
Fan P
1
,
Wang Q
1
,
Lu C1, Chen D1.This article reported that a 41-year-old female was referred for lumbago. She did not complain of any symptoms in the digestive system. DXA revealed high BMD in the lumbar vertebras. Marked increase in bone mass was observed in an X-ray of chest compared with one conducted 6 months previously. Additionally, an X-ray of the axial skeleton showed diffuse sclerotic change. Laboratory data revealed
hypocalcemia and high osteoblastic activity. A bone biopsy of the pelvis confirmed metastatic undifferentiated adenocarcinoma. Further research for the primary site revealed gastric signet ring cell carcinoma via endoscopic biopsy.
Slide50No
Shinkei
Geka
.
1989 Nov;17(11):1077-81.
[Osteoblastic skull metastasis of lung cancer].
[Article in Japanese]
Ueno M
1, Itakura T, Okuno T, Nakai K, Hayashi S, Komai N
A case of osteoblastic
skull metastasis of lung cancer is reported. A 56-year-old female patient was admitted to our hospital with complaints of headache and tumor of the right parietal bone. A plain skull X-ray showed
hyperostotic
feature of the right parietal bone. CT scan displayed that right parietal bone became thick and
osteoblastic
. Soft tissue was shown in the
hyperostotic
bone under MRI. An external carotid angiogram showed that the skull tumor was fed by the middle meningeal artery. The skull tumor and 2 solid
intracerebral
tumors were extirpated. Histological examination revealed adenocarcinoma in the skull and
intracerebral
lesions. The present case indicates that
osteoblastic
stimulating factor may be secreted by lung cancer.
Slide51Int
J Oral
Maxillofac
Surg.
2010 Mar;39(3):301-4
Mandibular
osteoblastic
metastasis of poorly differentiated carcinoma of the thyroid gland.
Nishikawa H
1, Nakashiro K, Sumida T, Sugita A, Hamakawa H.
An 83-year-old female presented with lower jaw swelling and pain. An elastic hard subcutaneous mass was observed in the median mandible. X-ray images confirmed a tumor lesion with periosteal reaction spreading radially from the mandible. A biopsy revealed nests of large, polygonal tumor cells growing in a supporting fibrovascular framework. The patient's anamnesis included thyroid carcinoma with lung metastasis, 2 years ago, treated by total
enucleation
of the thyroid and excision of the superior lobe of the left lung. Biopsy, primary and metastatic tumor samples all tested positive for thyroglobulin, suggesting a thyroid follicular epithelial origin. Mandibular metastasis of poorly differentiated carcinoma of the thyroid gland was diagnosed.
Slide52Oncogenic osteomalecia
Oncogenic
osteomalacia
is a rare metabolic bone disease characterized by phosphate leakage from the kidney and subsequent hypophosphatemia. It is caused by a
phosphaturic
factor produced by certain
tumours
. The disorder is characterized by hypophosphatemia (because of renal phosphate wasting), , decreased tubular phosphate reabsorption, increased serum alkaline phosphatase in the presence of
normal calcium
, 25(OH) vitamin D, and normal or slightly elevated serum pth. osteomalacia, bone pain, proximal muscle weakness, fractures, and functional disability . A reduction in circulating 1,25(OH)
2-vitamin D despite hypophosphatemia is the biochemical hallmark of the disease .OOM-inducing
tumours
are usually benign, arising either from bone or soft tissue, with extremities and craniofacial region being the most common sites..
Slide53BMC
Musculoskelet
Disord
.
2017 Sep 21;18(1):403.
Treatment and outcomes of tumor-induced
osteomalacia
associated with
phosphaturic mesenchymal tumors: retrospective review of 12 patients.Zuo QY
1, Wang H1,
Li W
1
,
Niu
XH
2
,
Huang YH
3
,
Chen J
1
,
You YH
4
,
Liu BY
5
,
Cui AM
6
,
Deng W
7
.
The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12
mmol
/L). Technetium-99m
octreotide
scintigraphy
was performed in 11 after having negative technetium-99m
octreotide
studies, underwent
18
F-fluorodeoxyglucose positron emission tomography/computed tomography (CT),
Slide54pseudohypoparathyroidism
Slide55Pseudohypoparathyroidism (PHP) refers to a group of heterogeneous disorders defined by targeted organ (kidney and bone) unresponsiveness to
PTh
PTH resistance is characterized by:
Hypocalcemia
Hyperphosphatemia
Elevated PTH concentrations
Slide56PHP-I is characterized by PTH resistance associated with a blunted
cAMP
and
phospahaturic
response to exogenous PTH.
PHP-
Ia
and PHP-
Ic
are clinically identical, sharing both the presence of AHO. AHO is absent in PHP-Ib patientsPhp-2 have normal or even elevated urinary cyclic adenosine monophosphate (AMP) concentrations in response to exogenous PTH administration but without a concomitant increase in phosphate excretion
Slide57Slide58Slide59Slide60Slide61Slide62BARTTER AND GITELMAN
Clinical manifestations
Bartter syndrome and
Gitelman
syndrome
are autosomal recessive disorders with
characteristic sets
of metabolic abnormalities that often presents in childhood and may be associated with the following clinical features:
Growth and mental retardationHypokalemiaMetabolic alkalosisPolyuria and polydipsia due to decreased urinary concentrating ability
Normal to increased urinary calcium excretionNormal or mildly decreased serum magnesium concentration Hypophosphatemia in occasional patients, with secondary
hyperparathyroidism being a possible mechanism
Slide63pathogenesis
Bartter syndrome is caused by TAL dysfunction and by inactivating mutation of each of its major transport proteins.
NKCC2 :
BARTTER
SYNDROM TYPE 1
ROMK:
BARTTER SYNDROM
TYPE 2
CLC-Kb:
BARTTER SYNDROM type3Barttin: BARTTER SYNDROM type4Reduced cl absorption in the loop of henle inhibits voltage driven paracellular absorption of ca, causing hypercalciuria
Slide64Classification
Types I and II are usually severe disorders that cause
polyhydramnios
during pregnancy and prematurity. Those who survive infancy develop hypokalemia , metabolic alkalosis, polyuria, and hypercalciuria .
Nephrocalcinosis
is common in patients and probably contributes to the late development of kidney
dysfunction
The classic form of Bartter syndrome, type III, is less severe and presents later in life with hypokalemia, metabolic alkalosis, and hypercalciuria. The reduced severity of type III Bartter syndrome may be due to redundancy of chloride channels in the cells-of the thick ascending limb.
Slide65CLASSIFICATION
Types IV and
IVb
have combined defects that involve both the
ClC-Ka
and
ClC
-Kb channels and cause severe disease, generally with antenatal presentation and congenital hearing loss. These two chloride channels are critical for normal ion transport in the
stria
vascularis of the inner ear and are vital to establish normal endocochlear potential differencesType V, usually called autosomal dominant hypocalcemia or autosomal dominant hypoparathyroidism, is due to a gain-of-function mutation in the CaSR .In the parathyroid gland, this results in a downward "resetting" of the normal range for serum calcium. As a result, a lower-than-normal serum calcium concentration inhibits parathyroid hormone release, resulting in hypocalcemia
Slide66Diagnosis
A newborn or a young child with vomiting ,dehydration , low-normal BP , sever hypokalemia , and metabolic alkalosis is likely to have barter syndrome if there is high urinary cl and k. the suspected diagnosis will receive further support if supplements of k and cl are inefficient in correcting the sever hypokalemia and BP.
Slide67Late-onset Bartter syndrome type II
Benjamin
Gollasch1, Yoland-Marie Anistan2, Sima Canaan-Ku¨ hl3
and
Maik
Gollasch2,3
A
43-year-old German woman was examined after incidental findings of bilateral
nephrocalcinosis by ultrasound during her second pregnancy hypokalaemia (3.0 mmol/L), Low normal total serum calcium (2.31 mmol/L), hyperaldosteronism (515ng/L, 847 ng/L) (normal range 30–340), hyperreninaemia(43.1ng/L, 25.6ng/L) (normal range 2.0–24.6)
increased calcium excretion in the urine [7.5mmol/day or 0.13mmol/kg bodyweight/day (normal range <6.2mmol/day or <0.1mmol/kg bodydescribe a female patient with a remarkably late-onset and mild clinical manifestation of BS II with compound heterozygous KCNJ1 missense mutations
Slide68Endocrine Society's 96th Annual Meeting and Expo, June 21–24, 2014 – Chicago
Late Onset Bartter's Syndrome Type 5, Successfully Treated with Recombinant PTH
Vipin Verma
1
,
Julianna Barsony
2
and
Priya Kundra
3 58- year old woman presented with dizziness, hand numbness, perioral tingling and syncope.ionized calcium (iCa) 0.71 (1.12-1.32 mmol/L)serum creatinine (Cr) 0.7 (0.5-1 mg/dl
intact PTH 25-35 (12-65 pg/ml), 25 OH vitamin D (D3) 27.4 (32-100 ng/ml)
magnesium (Mg) 1.3 (1.6-2.3 mg/dl)
potassium (K) 2.9 (3.5-5.1
mmol
/l)
bicarbonate 31 (22-30
mmol
/l).
Analysis of coding sequence of
CaSR
was performed, which showed heterozygous sequence variant with c.492+19G>A nucleotide change probably representing a gain-of-function mutation in our patient.