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In the name of GOD

This case study examines a 35-year-old woman with generalized musculoskeletal pain, weight loss, and metabolic abnormalities. The aim is to evaluate potential causes, including vitamin D deficiency, hypocalcemia, and celiac disease.

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In the name of GOD

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  1. In the name of GOD

  2. DrNoshin Ahmadi

  3. Patient identification • A 35 y/o woman ,single, from and living in Shahriyar, housewife • Chief complain: generalized musculoskeletal pain

  4. 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

  5. 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/dl • Vit D=8 ng/dl • Alb=4.4 g/dl • Esr=65 • pTH=475 pg/ml • Alkp =854 u/l

  6. Previous laboratory data(96/3-4) • 24hurine collection volum=1500 • Cr=16.35 mg/24h/kg • ca=109 mg/24h • p=1020 mg/24h • Hypokalemia and metabolic alkalosis

  7. Previous laboratory data • Wbc=7160 Hb=13.6 10.6 • mcv=85 Plt=433000 • Iron=45 tiBC=311 Ferittin=6 • Urea=33 cr=0.7 tsh=5.2 t4=5.6 • Aldestrone=169(30-400) • HLAB27=NEG • PANCA=NEG • CANCA=NEG • ANTI CCP=NEG

  8. Previous laboratory data • ANA=NEG • ANTI ENDOMISYAL AB=NEG • ANTI TTG=NEG • HbsAg=NEG • HCv AB=NEG • HIV 1,2 AB=NEG • WRIGHT=NEG

  9. Chest and abdomen pelvic ct • Normal except a 3-4 mm nodule in upper right lung lobe

  10. Bone densitometry

  11. ENDOSCOPY AND COLONOSCOPY • NORMAL

  12. EMG -NCV • 4 LIMBS- NORMAL

  13. From pubic ramus BIOPSY • Osteitisfibrosacystica

  14. Then she received calcium carbonate ,calciteriol , vitamin D, and POTASSIUM CHOLORIDE tab and referred to Taleghani hospital for more evaluation

  15. Past medical history • She has no history of illness • No cigarette smoking or alcohol use

  16. Familly history • No family history of metabolic disease • Mother has Htn controlled with oral drugs

  17. Review of system • Anorexia • Weigh loss about 10 Kg • One episode of hemoptysis during previous admission –not repetition • Spotting between regular menstruation

  18. 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 5/5 • No arthritis • No limitation of joint movement • GOVERN sign =positive

  19. 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

  20. Breast sonography • Mild fibrocystic change in both sides no obvious mass or lymphadenopathy is seen • Axillary lymph node is not seen

  21. Kidney sonography • Left kidney:123mm • Right kidney:122 mm • No stone , on hydronephrosis. No calcification

  22. 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 PTH • 25 hydroxyvit D=18 ng/dl (8 26 18) Low vitamin level • Ca=8.3mg/dl 9.3 8.2 • Ph=4.4md/dl 3.7 • Mg=2.4mg/dl • ESR=71 65 • K=2.6mg/dl 3 3.2 hypokalemia • Cr=0.8(GFR=74) • Uric acid=6.1 • Na=137mg/dl • Alb =4.4g/dl 3.8

  23. Wbc=8.7 /u • Rbc=3.9 • Hb=10.9 g/dl • Mcv=82 fl • Plt=547 *10*10*10 • Feritin=8 • Anti tpo=43 iu/ml

  24. Problem list • Musculoskeletal pain • Hypocalcaemia • High PTH • Hypophosphatemia • Vitamin D deficiency • Hypokalemia • Metabolic alkalosis • 10 Kg weight loss • High EsR • IDA

  25. Major causes of hypocalcaemia with high PTH vitamin D deficiency or resistance Pth resistance(missense mutation ,pseodohypoparathyroidism, hypomagnesemia) Renal disease Loss of calcium from the circulation Drugs Disorders of magnesium metabolism

  26. 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

  27. 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

  28. Celiac diagnosis • The serologic test (IgA-tTG) could be falsely negative. IgA or IgGgliadin 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 present • Non-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

  29. 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

  30. Loss of calcium from circulation • Hyperphosphatemia • Tumor lysis syndrome • Acute pancreatitis • Acute respiratory alkalosis • Acute sever illness • Osteoblastic metastasis

  31. 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.

  32. 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

  33. 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 P1, Wang Q1, 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.

  34. No ShinkeiGeka. 1989 Nov;17(11):1077-81.[Osteoblastic skull metastasis of lung cancer].[Article in Japanese]Ueno M1, 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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