In the name of GOD Dr Noshin - PowerPoint Presentation

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In the name of GOD

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Dr Noshin

Ahmadi

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Patient identification

A 35 y/o woman ,single, from and living in

Shahriyar

, housewife

Chief complain: generalized musculoskeletal pain

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Present 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

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Previous 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

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Previous 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

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Previous 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

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Previous laboratory data

ANA=NEG

ANTI ENDOMISYAL AB=NEG

ANTI TTG=NEG

HbsAg

=NEG

HCv

AB=NEG

HIV 1,2 AB=NEG

WRIGHT=NEG

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Chest and abdomen pelvic

ct

Normal except a 3-4 mm nodule in upper right lung lobe

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Bone densitometry

T score

Z score

L1-L4

-2.8

-2.8

TOTAL

-3

-2.9

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ENDOSCOPY AND COLONOSCOPY

NORMAL

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EMG -NCV

4 LIMBS- NORMAL

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From pubic ramus

BIOPSY

Osteitis

fibrosa

cystica

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Then she received calcium carbonate ,calciteriol , vitamin D, and POTASSIUM CHOLORIDE tab and referred to

T

aleghani

hospital for more evaluation

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Past medical history

She has no history of illness

No cigarette smoking or alcohol use

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Familly history

No family history of metabolic disease

Mother has

Htn

controlled with oral drugs

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Review of system

Anorexia

Weigh loss about 10 Kg

One episode of hemoptysis during previous admission –not repetition

Spotting between regular menstruation

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PHYSICAL 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

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Thyroid 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

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Breast sonography

Mild fibrocystic change in both sides no obvious mass or lymphadenopathy is seen

Axillary lymph node is not seen

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Kidney sonography

Left kidney:123mm

Right kidney:122 mm

No stone , on

hydronephrosis

. No calcification

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Laboratory 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

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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

Slide38

Problem list

Musculoskeletal pain

Hypocalcaemia

High PTH

Hypophosphatemia

Vitamin D deficiency

Hypokalemia

Metabolic alkalosis

10 Kg weight loss

High EsRIDA

Slide39

Major 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

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CELIAC

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

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Atypical 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

Slide43

Celiac 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

Slide44

Endocr 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

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Loss of calcium from circulation

Hyperphosphatemia

Tumor

lysis

syndrome

Acute pancreatitis

Acute respiratory alkalosis

Acute sever illness

Osteoblastic metastasis

Slide47

Osteoblastic 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.

Slide48

Turk 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

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Postgrad 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.

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No

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.

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Int

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.

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Oncogenic 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..

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BMC

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),

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pseudohypoparathyroidism

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Pseudohypoparathyroidism (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

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PHP-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

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BARTTER 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

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pathogenesis

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

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Classification

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.

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CLASSIFICATION

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

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Diagnosis

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.

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Late-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

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Endocrine 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.