Orris

Patient: Mrs. Sushma Sanjeev Chintal 66-year-old Female Physical Baseline: Height 142 cm; Stable weight (33–36 kg) for 45 years. **Medical History*: Cesarean Delivery – 2 times ; Cataract both eyes 2018 Pulmonary Tuberculosis (1993); successfully treated with no relapse *October 2021* Diagnosed with osteoporosis Denosumab d3 and ca given Na/k normal **May 2023 ** Admitted for hyponatramia No documents available *April 2024* Spinal fractures detected *18F-FDG PET/ct scan* Hypermetabolic areas of consolidation with surrounding centrilobular nodules in medial and lateral segments of right middle lobe, lateral basal segment of right lower lobe and posterior and lateral basal segments of left lower lobe, appears infective. Low-grade metabolism in the superior endplate of L1 and L2 vertebral bodies with mild collapse, suggestive of osteoporotic fractures. Other incidental benign findings are as described. No other significant abnormality or metabolically active relevant disease seen elsewhere in the body to suggest neoplastic disease. Antibiotics has been given **May 2024 ** Episode of hyponatramia Siadh label Urinary na 118 Serum osmolality 264 Urinary osmolality not found in reports Dr gautam javeri adv denuzumab 60mg 6monthly 7 dose taken last dose taken 15/4/2026 Pt admitted with electrolytes imbalance 2 to 3 times Every time treated with tolvaptan *July 2025* Hb - 7.8 Iv iron Carboxymaltose given *Dec 2025* Adm for abdo pain Gastrin : 104pg/ml Chromogranin A - 1398 Urinary 5-hiaa - 10.74 mg/24hrs Imaging: Ga-68 DOTATATE PET-CT (DOTA Scan) performed on December 12 at RMC/Tata Hospital was unremarkable (normal). Admitted with abdo pain multiple times Ugi scopy and colonoscopy done twice *May 2024* Antral gastitis *Jan 2026* Grade 1 Esophageal Candidiasis treated with fluconazole And multiple haemorrhoids Thyroid profile is normal Hgt are normal *24/4/26* Tsh/t3/t4 - 1.18/4.6/16.2 D3 - 22.1 B12 - 330 Pth - 80.5 8am cortisol - 41.63 Chromogranin a - 1109 was 73.74 on 9th of feb Gastrin - 931 was 47.1 on 9th feb *Repeat DOTA PET-CT at Jaslok Hospital (April 26).* No evidence of somatostatin receptor expressing disease is seen anywhere in the body. SEVERE DEGENERATIVE CHANGES ARE SEEN IN THE THORACIC AND LUMBAR VERTEBRAL BODIES WITH NO ABNORMAL SSTR EXPRESSION. Recent Procedure: Endoscopic Ultrasound (EUS) with fine-needle biopsy negative for malignancy *Mri spine (11/05/2026)* Pathological fracture of multiple vertebrae *29/07/2026* Lft - normal Hb/wbc/plt - 14/6.52/326 Na/k/cl - 124.2/4/86.4 Uric acid - 1.56 Ca/po4 - 9.32/2.44 Pth - 119 **30/7/26 ** Ca/na - 8.32/127.9 2d echo 60% ef No rwma **Bmd dexa scan ** 3 times Shows osteoporosis **Present complain ** Back pain since 2 years Walking with help of support (walker) since last 6 months radiating to both legs Pt is non diabetic with normal thyroid function test and also not on any diuretics No symptoms of volume overload Bowel bladder not involved Power b/l lower limb- 3/5 All Reflex +1 Planter flexors Emg - suggestive of left superficial peroneal sensory mono neuropathy **Current medication ** Inj. Bonvista S/C OD (Teriparatide) daily for 3 months has been taken last dose 17/6/2026 Inj. Denu 60 (Every 6 months since Oct 2022) Completed 7 doses Last dose on 15 April 2026. One dose of romosozumab taken Tab addana (na chloride) 1gm 1-0-1 Tab natrise (tolvaptan) 15mg 1-0-0. Tab shelcal xt 0-1-0 One dose of romosozumab taken Sx is C arm guided percutaneous bone cementing multiple level Key qus Why bisphosphonate not given by anyone ?? Cause of repeated hyponatramia not known ? What can we give for osteoporosis to prevent future fractures??? Why gastrin and chromogranin a is high with normal ga-68 dotatate pet scan??

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SIADH hyponatremia causes recurrent elderly

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denosumab osteoporosis sequential therapy romosozumab teriparatide

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chromogranin A gastrin elevated negative somatostatin receptor PET

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chromogranin A false positive elevated causes non-neuroendocrine

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denosumab discontinuation bisphosphonate transition rebound vertebral fracture

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chromogranin gastrin PPI proton pump inhibitor elevation neuroendocrine

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chromogranin A elevated gastrin high negative DOTATATE PET scan causes PPI renal failure false positive 2024

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adrenal insufficiency SIADH hyponatremia cortisol low

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why bisphosphonates avoided with SIADH hyponatremia denosumab preferred osteoporosis 2024 guidelines

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osteoporosis bisphosphonate after denosumab discontinuation zoledronate transition

The full analysis is above. Here is a structured final summary:

Clinical Analysis - Mrs. Sushma Sanjeev Chintal (66F)

Q1: Why Was a Bisphosphonate Never Given?

Multiple legitimate reasons converged:
GI contraindications to oral bisphosphonates:
  • Grade 1 esophageal candidiasis (Jan 2026)
  • Antral gastritis (May 2024)
  • Multiple admissions for abdominal pain Oral bisphosphonates (alendronate/risedronate) require fasting ingestion with large water volumes, strict upright posture, and carry significant esophagitis risk - all contraindicated in her GI profile.
IV Zoledronate was the missed opportunity - it bypasses all GI concerns, given once yearly. It was likely not initiated because of unresolved hyponatremia workup, low weight/frailty concerns, and clinical attention being diverted to the NET scare.
The current emergency: Her last denosumab dose was April 15, 2026 - she is now 3.5 months post-discontinuation with no bridging bisphosphonate. FREEDOM trial data (PMID 36088628) and a 2024 JAMA Network Open RCT (PMID 39527056) confirm that multiple vertebral fractures occur in patients stopping denosumab without a bisphosphonate bridge - she is already in this high-risk window with documented pathological spinal fractures.

Q2: Cause of Recurrent Hyponatremia - The Missed Diagnosis

The single most important finding in all her data: 8 AM Cortisol = 41.63 nmol/L (~1.5 mcg/dL)
Normal 8 AM cortisol: >400 nmol/L. This value is critically low and indicates adrenal insufficiency (AI) - a fully treatable, reversible cause of all her hyponatremia that has been misclassified as "SIADH."
Mechanism: Cortisol normally suppresses vasopressin (ADH). Without cortisol, ADH is constitutively elevated, causing water retention and dilutional hyponatremia - a state that biochemically mimics SIADH (euvolemic, low serum osmolality, elevated urinary sodium) but is a fundamentally different condition requiring different treatment.
Why TB is the link: Pulmonary TB (1993) can cause primary adrenal insufficiency (Addison's disease) by adrenal gland destruction - even 30+ years later via calcification and fibrosis. This is a classic association.
Action needed urgently:
  1. Plasma ACTH level (paired with cortisol)
  2. Short Synacthen (ACTH stimulation) test - gold standard
  3. Adrenal CT - look for calcification, atrophy from old TB
  4. If confirmed AI: Hydrocortisone replacement will likely resolve the hyponatremia, allowing tolvaptan to be tapered and stopped
Other contributors to consider: her pulmonary consolidation lesions (seen on PET April 2024) still need definitive diagnosis - active or recurrent TB/atypical infection can itself cause SIADH as well as damage adrenals further.

Q3: What to Give for Osteoporosis to Prevent Future Fractures?

Step 1 - IMMEDIATE: IV Zoledronic Acid 5 mg infusion
  • Check GFR first (contraindicated if <35 mL/min)
  • Correct vitamin D to >30 ng/mL before/alongside (currently D3 22.1 - give 60,000 IU weekly cholecalciferol x 8-12 weeks)
  • This bridges the denosumab discontinuation and prevents catastrophic rebound fractures
  • A 2026 meta-analysis (PMID 41105226) and ACP 2023 guidelines endorse bisphosphonates as first-line and as essential post-denosumab bridging therapy
Step 2: Complete Romosozumab Course (if CV risk acceptable)
  • Most potent anabolic agent; 210 mg SC monthly, 12 doses total (she has had only 1)
  • EF 60% preserved - reassuring, but formal CV risk assessment needed given romosozumab's boxed warning for cardiovascular events
  • After 12 doses, transition to antiresorptive (zoledronate annually)
Step 3: Vitamin D and PTH management
  • D3 22.1 - insufficient; target >40 ng/mL for osteoporosis management
  • PTH 119 - secondary hyperparathyroidism driven by low D3/low calcium; should normalize with D3 correction
  • Shelcal XT (calcium + D3) - continue
Note on teriparatide: 3 months is too short (recommended 18-24 months). But given she has also received romosozumab and the anabolic "slot" is ideally occupied by romosozumab for now, reinitiate teriparatide only if romosozumab is contraindicated.

Q4: Why is Gastrin + CgA High with Normal DOTATATE PET?

Almost certainly PPI-induced false elevation - not a NET.
The timeline is the key diagnostic clue:
  • February 9, 2026: Gastrin 47.1 pg/mL (normal), CgA 73.74 (normal)
  • April 2026: Gastrin 931, CgA 1109 - a 20-fold rise in 6 weeks
No genuine NET behaves this way. A 2023 PMC case report documented a 10-fold CgA rise with negative DOTATATE PET purely from PPI use. A Frontiers in Endocrinology study found PPI use accounted for the majority of false-positive CgA and gastrin elevations at a specialist NET center.
Mechanism: PPIs block gastric acid → G-cells release more gastrin (loss of acid-feedback suppression) → gastrin causes ECL cell hyperplasia → ECL cells secrete CgA in proportion to their number and stimulation. No tumor required.
Her specific triggers:
  • Esophageal candidiasis (Jan 2026) - PPI likely started or escalated
  • Antral gastritis - ongoing PPI indication
  • The rise from Feb to April exactly matches when PPI use would have been increased for GI complaints
Additional non-NET causes of CgA elevation to note:
  • Chronic atrophic gastritis (she has gastritis)
  • Adrenal insufficiency (stress-state)
  • Renal impairment (GFR unknown - needs checking)
  • Heart failure (EF preserved - less likely)
Action:
  1. Stop or hold PPIs for minimum 14 days
  2. Retest CgA and gastrin in fasting state after PPI cessation
  3. If they return toward her Feb 2026 normal values, false-positive is confirmed - no further NET workup needed
  4. Borderline urinary 5-HIAA (10.74, normal <8 mg/24h) - repeat under strict dietary restrictions (no bananas, tomatoes, nuts, avocado, walnuts 48h before collection) before concluding it is truly elevated
Both negative DOTATATE PETs, negative EUS biopsy, and a normal February 2026 baseline are highly reassuring against a neuroendocrine tumor.

Unified Clinical Picture

The connecting thread that ties all four problems together is likely adrenal insufficiency from TB-damaged adrenals:
  • Low cortisol → persistent ADH → recurrent hyponatremia misread as SIADH
  • Cortisol deficiency → impaired osteoblast function → worsened bone loss
  • Stress physiology from untreated AI → elevated CgA
  • Frailty and weakness attributed to osteoporosis and neuropathy may partly be hypocortisolism
A unified endocrinology review is the single most important next step.
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