A case of

hypercalcemia
A case presentation by cabalona, demecillo, escarda,
salazar, yano

General objective:
To present a case of C.N., a 40-year old, male, presenting
with
hypercalcemia

Specific objectives:
To be able to present the patients profile, history of present illness,
physical examination and clinical formulation,
To be able to present the patients course in the ward,
To be able to discuss the etiology, pathogenesis, diagnosis, clinical

manifestations and management of the hyperparathyroidism,

To be able to discuss the current diagnostic evaluation and
treatment

recommended for the patients disease.

Patients Profile
C.N.
40/M
Married, Filipino, Roman Catholic
Security guard
Cabantan St., Barrio Luz, Cebu City
Admitted for the 1st time on June 23, 2015
reason for admission: hypercalcemia

History of present illness

4
months
PTA

sought consult at CHH for recurrent attack of gouty arthritis

work-up was done which revealed a high serum creatinine level
- unrecalled level
referred to a nephrologist
additional labs were taken which revealed high calcium level
unrecalled level
(-) fever, dyspnea, nausea and vomiting or changes in bladder
and bowel habits
no medications taken

History of present illness

4
months
PTA

2
months
PTA

Patient went back to his doctor for follow-up. A series of labs were done.

Whole abdominal ultrasound:

Diffuse fatty changes of the liver

Cholelithiasis without evidence of cholecystitis
Nephrocalcinosis with nephrolithiasis of both kidneys
Bilateral simple renal cortical cysts
Enlarged prostate gland (Grade I) with no calcification

UTZ of the neck

Slightly enlarged thyroid gland and multifocal lesions probably
adenomatous/colloid/hyperplasia, some undergoing cystic degeneration,
seen on a
background with normal thyroid parenchyma
consider parathyroid nodules vs enlarged para-tracheal lymph nodes,
inferior, superior
portions, R side

April 7, 2015
Test

Result

Reference range

Urea nitrogen

34.8 mg/dl

7.0-18.0

Creatinine

7.2 mg/dl

0.6-1.5

Ionized calcium

1.9 mmol/L

0.9-1.4

Test
Intact PTH

Result
921.1 pg/ml

Reference range
Male: 15-65

April 8, 2015
Test

Result

Reference range

Urea nitrogen

33.4 mg/dl

7.0-18.0

Creatinine

5.7 mg/dl

0.6-1.5

Uric acid

7.5 mg/dl

3.0-8.0

Albumin

3.5 g/dl

3.5-5.0

Total calcium

12.9 mg/dl

8.4-10.4

Test
Thyroid function test
FT4
FT3
TSH

Result

9.13 pmol/l
4.25 pmol/l
0.757 IU/ml

Reference range
Male: 15-65
11.0-22.5
3.1-6.5
0.30-5.0

April 10, 2015

Test

Result

Reference range

Urea nitrogen

37.2 mg/dl

7.0-18.0

Creatinine

5.9 mg/dl

0.6-1.5

Total Calcium

13.5 mg/dl

8.4-10.4

Sodium

138.0 mmol/l

134-148

Potassium

4.3 mmol/l

3.3-5.3

April 11, 2015

Test
Total Calcium
Test
Thyroid function test
FT4

Result
13.2 mg/dl
Result
10.68 pmol/l

Reference range
8.4-10.4
Reference range
11.0-22.5

April 20, 2015

Test

Result

Reference range

Total Calcium

12.2 mg/dl

8.4-10.4

Potassium

5.3 mmol/l

3.3-5.3

April 20, 2015

Test

Result

Reference range

Urea nitrogen

49.9 mg/dl

7.0-18.0

Creatinine

5.3 mg/dl

0.6-1.5

Albumin

2.4 g/dl

3.5-5.0

Total Calcium

13.7 mg/dl

8.4-10.4

Potassium

3.8 mmol/l

3.3-5.3

History of present illness

4
months
PTA

2
months
PTA

Patient went back to his doctor for follow-up. A series of labs were done.
Advised admission & surgery

Past Medical History

Hypertensive for 16 years now,
HBP: 200/120 mmHg, UBP: 160/80 mmHg
Metoprolol (Neobloc) 50mg/tab 1 tab OD PO, poor compliance
Non-diabetic, non-asthmatic
No known food and drug allergies
Abdominal hernia repair unrecalled year
Renal stones 25 yo, passed out grain sized white hard stones
Gouty arthritis 27 yo, self-medicated with Ibuprofen (Alaxan FR), Diclofenac
Athrocentesis of the left knee 2013

Personal/Social history
Former hotel attendant in Riyadh, Saudi Arabia for 6 years
Currently a security guard at Marriott Hotel
Former cigarette smoker with 25.5 pack year history
Former heavy alcoholic beverage drinker; drank 3x a week to the point of
intoxication
stopped last 2014
History of Methamphetamine and Cannabis use
Usual diet consists of rice, vegetables and fish, rarely meat; Water
intake: 3-5 L of water
No herbal supplements
Urinates > 10 times per day; Regular bowel movement

Heredofamilial diseases
Hypertension, Diabetes, Bronchial asthma paternal
& maternal
Prostate cancer paternal
Parathyroid pathologies paternal
Thyroid cancer - Mother

Review of Systems
General: recent weight loss of approximately 30 kilograms in 1 year
Skin: dry, (-) rashes, lumps, sores, pruritus, changes in color, changes in the hair or nails
Head: (-) headache, head trauma, dizziness, and lightheadedness
Eyes: (-) vision changes, eye pain , redness, excessive tearing, blurred vision,
development of cataracts, glaucoma
Ears: (-) tinnitus, vertigo, ear pain, infections and discharges
Nose and Sinuses; (-) frequent colds, nasal congestion, discharges, sinusitis
Mouth and Throat: (-) cyanosis, dry mouth, bleeding gums, sore throat, hoarseness

Review of Systems
Neck: (-) history of goiter, (-) palpable lumps, lymph nodes and neck
stiffness
Respiratory: (-) cough, hemoptysis, dyspnea, wheezing
CVS: (-) high blood pressure, rheumatic fever, heart murmurs, PND
GI: polydipsia, (-) nausea, vomiting, polyphagia; (-) dysphagia, heartburn,
changes in bowel habits, anorexia
GUT: (+) polyuria, nocturia; (-) urinary urgency, dysuria, hematuria,
incontinence, dribbling and hesitancy
PVS: (-) Intermittent claudication, cramping, tingling and numbness,
varicosities

Review of Systems
MS: (+) joint pain on both knees, (-) weakness, (-)muscle pains, stiffness,
history of trauma
CNS: (-) changes in sensorium, syncope, seizures, paralysis, numbness or
loss of sensation, and aphasia
Hematologic: (-) anemia, easy bruising, prolonged bleeding , blood
transfusions
Endocrine: (-) history of goiter; (-) Diabetes
Psychiatric: (-) history of psychiatric illnesses

Physical Examination
General survey: Awake, alert, afebrile, sthenic, not in respiratory
distress
Vital signs: T: 36.8 degrees Celsius, RR: 22 cpm, PR: 102 bpm, BP:
120/80 mmHg
Skin: Warm, Dry , Rough, Senile turgor, No lesions
HEENT: No gross deformities, No lesions on the scalp, Equal palpebral
fissures, white sclerae, pink palpebral conjunctivae, clear lens, equally
round and reactive pupil, no nasoaural discharges, pink, moist lips,
normal oral mucosa, non inflamed tonsils
Neck: Supple, trachea at midline, non-palpable thyroid, no engorged
neck veins

Physical Examination
Chest and lungs: no gross deformities, no abnormal retractions,
no areas of tenderness, resonant, clear breath sounds, (-) rales,
(-) wheeze
CVS: adynamic precordium, PMI located at the 5th LICS MCL, <
2.5 cm in diameter, distinct S1&S2 sounds, HR: 106 bpm, no
murmur
Abdomen: flabby, 5 cm linear supra-umbilical scar, normoactive
bowel sounds, generally tympanitic except at area of liver
dullness (LAD: 4CM-MSL, 8CM-MCL); soft and nontender; no
organomegaly
GUT: (-) KPS bilaterally
Extremities: (+) Grade 1 bipedal pitting edema, no gross
deformities, CRT < 2 seconds, strong peripheral pulses, no

Physical Examination
CNS: Alert, coherent and oriented to 3 spheres: time, place and
person
Cranial nerves 1 Intact sense of smell
2,3(+) pupillary light reflex, direct and consensual, OU
3,4,6 Full range of EOM in 6 cardinal positions
5 Facial sensations intact; muscle of mastication strong
7 Intact facial expressions, symmetrical facial features
8 Able to hear and repeat spoken words at 2 feet distance both ears
9,10 Intact gag reflex

Physical Examination
11 Able to turn head and shrug shoulders against resistance
12 Midline tongue at rest and protrusion
Well coordinated movement by finger to nose test and heelshin
test
Intact sense of light touch, pain and temperature
No atrophy or fasciculations
5/5 in all extremities
+2 on all extremities; (-) Babinski

Salient Features:
History
Hypertensive
Former cigarette smoker with 25.5 pack year history
Heavy alcoholic beverage drinker; drinks 3x a week to the point
of intoxication,
stopped last 2014
No use of herbal supplements

ROS:
Recent weight loss of approximately 30
kg in 1 year
RR: 22 cpm, PR: 102 bpm
Skin: warm & dry
GI: polydipsia
GUT: polyuria, nocturia
Extremities: (+) Grade 1 bipedal pitting
edema

Labs:
UTZ of the neck: slightly
enlarged thyroid
gland & multifocal lesions
Labs: high serum creatinine,
ionized Ca2+,
intact PTH

Clinical Formulation
Primary impression: Hyperparathyroidism secondary to
parathyroid
Risk adenoma
factors, signs and
Remarks
symptoms

History of passing out of stones

in urine

polyuria

Polydipsia

Weight loss

Anorexia

Nausea and vomiting

constipation

fatigue

Neck mass

Family history of parathyroid

Clinical Formulation
Laboratory results

Remarks

Ultrasound of the neck

increased Intact PTH

Increased totcal calcium

Increased ionized calcium

Differential diagnosis:
Hyperparathyroidism secondary to CKD secondary to obstructive uropathy
secondary to renal stones
Risk factors, signs and
symptoms

Remarks

anorexia

anuria

Bipedal edema

hypertension

pallor

Peripheral neuropathy

Nausea and vomiting

History of passing out stone in

urine

History of flank pain

Differential diagnosis
Laboratory results

Remarks

Elevated BUN

Elevated serum creatinine

hyperkalemia

nephrocalcinosis

Elevated PTH

hypercalcemia

Differential diagnosis:
Hyperparathyroidism secondary to parathyroid carcinoma
Risk factors, signs and
symptoms

Remarks

History of passing out of stones

in urine

polyuria

polydypsia

Weight loss

Anorexia

Nausea and vomiting

constipation

fatigue

Neck mass

Family history of parathyroid

Laboratory results

Remarks

Ultrasound of the neck

increased Intact PTH

Increased totcal calcium

Increased ionized calcium

Differential diagnosis:
Hypercalcemia of malignancy
Risk factors, signs and
symptoms

Remarks

Family history of malignancy

Smoker

Alcoholic beverage drinker

Advancing age

Exposure to radiation

Diagnostics:
UTZ of the neck
Thyroid panel
Serum PTH
Serum total and ionized calcium, albumin, phospohorous, BUA,
crea, K, ABG
Urinalysis, 24 hour urine collection
CBC
12L ECG

Therapeutic management:
Venoclysis: 1L PNSS at 30cc/hr
Diet: low salt, low fat, low purine diet
Medications:
Levothyroxine 100mcg/tab 1 tab OD PO
Metoprolol 50mg/tab 1 tab OD PO
Losartan 50mg/tab 1 tab OD PO
Sodium bicarbonate 650mg/tab 1 tab OD PO
Febuxostat 40mg/tab OD PO
Ketoanalogue 1 tab TID PO

Case discussion

Hyperparathyroidism
Generalized disorder of calcium, phosphate, and bone
metabolism due to an increased secretion of PTH
Nephrolithiasis, peptic ulcers, mental changes, and,
less frequently, extensive bone resorption
Annual incidence of the disease is calculated to be as
high as 0.2% in patients >60
Peak: 30s-40s
Estimated prevalence, including undiscovered
asymptomatic patients of 1%

Hyperparathyroidism

Etiology
Solitary adenomas
80% of patients single abnormal gland
benign neoplasm or adenoma and rarely a parathyroid carcinoma
15% of patients, all glands are hyperfunctioning

Hereditary syndromes
MEN1
MEN 2A, 2B
HPT-JT

Pathology
Adenomas are most often located in the inferior
parathyroid glands
610% of patients - thymus, the thyroid, the pericardium,
or behind the esophagus
Parathyroid carcinoma is often not aggressive.
Hyperparathyroidism from a parathyroid carcinoma may
be indistinguishable from other forms of primary
hyperparathyroidism but is usually more severe clinically.
Calcium values of 3.53.7 mmol/L (1415 mg/dL) are
frequent with carcinoma

Lithium therapy
~10% of treated patients
long-standing stimulation of parathyroid cell
replication by lithium may predispose to development
of adenomas
higher calcium levels are required to lower PTH
secretion, probably acting at the calcium sensor

Familial Hypocalciuric
hypercalcemia
autosomal dominant trait
inactivating mutation in a single allele of the calcium
sensing receptor, third family of GCPRs
The primary defect is abnormal sensing of the blood
calcium by the parathyroid gland and renal tubule,
causing inappropriate secretion of PTH and excessive
renal reabsorption of calcium

Jansens disease
Activating mutations in the PTH/PTHrP receptor
(PTH1R)
short-limbed dwarfism due to abnormal regulation of
chondrocyte maturation in the growth plates of the
bone that are formed through an endochondral process
adult life, there are numerous abnormalities in bone,
including multiple cystic resorptive areas
Hypercalcemia and hypophosphatemia with
undetectable or low PTH levels are typically seen

Malignancy related
hypercalcemia
20% of cancer patients, especially with certain types
of tumor such as lung carcinoma
PTHrP is the responsible humoral agent in most solid
tumors that cause hypercalcemia
histologic character of the tumor is more important
than the extent of skeletal metastases in predicting
hypercalcemia

Malignancy related
hypercalcemia
Mechanisms:
Production of PTHrP
Direct bone marrow invasion
increased blood level of 1,25(OH) 2 D lymphomas

Vitamin D intoxication
Chronic ingestion of 40100 times the normal
physiologic requirement of vitamin D (amounts
>40,000100,000 U/d
The diagnosis is substantiated by documenting
elevated levels of 25(OH)D >100 mg/mL.
However, vitamin D stores in fat may be substantial,
and vitamin D intoxication may persist for weeks after
vitamin D ingestion is terminated
Responsive to glucocorticoids, which in doses of 100
mg/d of hydrocortisone

Sarcoidosis and other

granulomatous disease
Tuberculosis and fungal infections
Excess 1,25(OH) 2 D is synthesized in macrophages or
other cells in the granulomas
Management of the hypercalcemia can often be
accomplished by avoiding excessive sunlight exposure and
limiting vitamin D and calcium intake.
Glucocorticoids in the equivalent of 100 mg/d of
hydrocortisone or equivalent doses of glucorticoids may help
control hypercalcemia.

Hyperthyroidism
20% of hyperthyroid patients have high-normal or
mildly elevated serum calcium concentrations
Hypercalciuria is even more common
Thyroid-stimulating hormone (TSH) itself normally has
a bone protective
Hypercalcemia is managed by treatment of the
hyperthyroidism.

Immobilization
Cause hypercalcemia in children and adolescents esp.
after spinal cord injury and paraplegia or quadriplegia
Decreased bone formation and increased bone
resorption
Hypercalcemia resolves with resumption of
ambulation

Thiazides
Inhibits reabsorption of Na and Cl from distal convoluted
tubules by blocking Na CL symporter
By lowering the Na concen. Within the epith. Cells,
thiazides increase the activity of the Na/Ca antiporter on
the basolateral membrane to transport more Ca into the
interstitium then diffuse into the cell via TRPV5
Chronic administration enhance proximal tubular
resorption of sodium and calcium in response to sodium
depletion leads to reduction in urinary calcium

Vitamin A intoxication
Side effect of dietary faddism
Calcium can be elevated to 3-3.5mmol/L (12-14mg/dL)
after ingestion of 50,000-100,000 units of vitamin A
daily
Fatigue, anorexia, severe muscle and bone pain
Tx:
withdrawal of the vitamin
administer 100mg/d hydrocortisone

Severe Secondary hyperparathyroidism

Resistance to normal level of PTH - develop hypocalcemia

stimulate parathyroid enlargement
Increase FGF23 production, a potent inhibitor of renal 1alpha hydroxylase
FGF23 dependent reduction in 1,25(OH)2 vitamin D
Development of secondary hyperparathyroidism
hypocalcemia most common initiating factor for
secondary hyperparathyroidism

Severe Secondary hyperparathyroidism

may also occur in those with osteomalacia d/t deficiency of

vitamin D action
bone pain, ectopic calcification and pruritus
renal osteodystrophy- bone disease in pt. with secondary
hyperparathyroidism and chronic kidney disease.
TX:
use nonabsorbable antacids + calcitriol (0.25 2ug/d)
reduction of excessive blood phosphate by dietary phosphate
restriction
IV calcitriol administered as several pulses each week

Tertiary hyperparathyroidism
state of severe hyperparathyroidism in patients with
renal failure that requires surgery
- TX: parathyroid surgery

Aluminum intoxication
Occurs in patients on chronic dialysis
Acute dementia, unresponsive and severe
osteomalacia, bone pain, multiple nonhealing fractures
on ribs and pelvis, proximal myopathy
Hypercalcemia develops when treated with vitamin D
and calcitriol due to impaired skeletal responsiveness

Aluminum intoxication
Aluminum is present at site of osteoid mineralization,
osteoblastic
activity is minimal, calcium incorporation to bone is
impaired
TX: avoid aluminum-containing antacids or aluminum
excess in the
dialysis regimen.

Milk alkali syndrome

Due to excessive ingestion of calcium and absorbable
antacids (ex. Milk or calcium carbonate) May be
categorized as acute, subacute and chronic (aka.
Burnetts syndrome)

Features:
Hypercalcemia
Contributes to alkalosis
PTH secretion

Mild hypercalcemia Suppress

Causes increased sodium excretion and

some depletion of total body water
Increased bicarbonate resorption

Alkalosis
Enhances calcium resorption in distal nephron
Aggravates hypercalcemia
Renal failure

Signs and symptoms

One-half or more of patients with hyperparathyroidism
are asymptomatic

Renal
Polydipsia
Polyuria
Renal stones

Cardiovascular
Left Ventricular hypertrophy
Cardiac functional defects
Endothelial dysfunction

Gastrointestinal

Abdominal distress
Constipation
Vomiting
Anorexia
Weight loss

Musculoskeletal
Osteitis fibrosa cystica
025% of patients reported 50 years ago
giant multinucleated osteoclasts in scalloped areas
on the surface of the bone (Howships lacunae) and a
replacement of the normal cellular and marrow
elements by fibrous tissue
subperiosteal resorption

Musculoskeletal
Cortical bone density is reduced while cancellous bone
density,
especially in the spine, is relatively preserved
Neuromuscular manifestations may include proximal
muscle
weakness, easy fatigability, and atrophy of muscles

CNS

Anxiety
Depression
Psychosis
Apathy
Fatigue

Diagnosis
Elevated PTH level
Serum calcium
Serum phosphate is usually low but may be normal

Diagnosis

Treatment
Surgical excision of the abnormal parathyroid tissue
- definitive therapy
Neck exploration
Minimally-invasive parathyroidectomy

Treatment
A decline in serum calcium occurs within 24 hours after
successful surgery; usually blood calcium falls to lownormal values for 35 days until the remaining
parathyroid tissue resumes full hormone secretion
In general, there are few problems encountered in
patients with uncomplicated disease such as a single
adenoma (the clear majority)

Treatment
Signs of hypocalcemia include symptoms such as
muscle twitching, a general sense of anxiety, and
positive Chvosteks and Trousseaus signs coupled with
serum calcium consistently <2 mmol/L (8 mg/dL).
Parenteral calcium replacement at a low level should be
instituted when hypocalcemia is symptomatic. An
infusion of 0.52 mg/kg per hour or 30100 mL/h of a 1mg/mL solution usually suffices to relieve symptoms

Treatment
Medical surveillance without operation for patients with
mild, asymptomatic disease

Treatment
Preoperative 99m Tc sestamibi scans with singlephoton emission CT (SPECT) are used to predict the
location of an abnormal gland and intraoperative
sampling of PTH before and at 5-minute intervals after
removal of a suspected adenoma to confirm a rapid fall
(>50%) to normal levels of PTH

Hypercalcemic states

Hypercalcemic state
The first principle of treatment is to restore normal
hydration
Increasing urinary sodium excretion to 400500 mmol/d
increases urinary calcium excretion even further than
simple rehydration.
After rehydration has been achieved, saline can be
administered or furosemide or ethacrynic acid can be
given twice daily to depress the tubular reabsorptive
mechanism for calcium

Biphosphonates
Analogues of pyrophosphate, with high affinity for bone, especially
in areas of increased bone turnover, where they are powerful
inhibitors of bone resorption.
Etidronate, was effective but had several disadvantages, including
the capacity to inhibit bone formation as well as blocking
resorption.
Pamidronate 30-90mg IV single dose
Zolendronate given in doses of 4 or 8 mg/5-minute infusion has a
more rapid and more sustained effect than pamidronate in direct
comparison

Calcitonin
Acts within a few hours of its administration,
principally through receptors on osteoclasts
After 24 hours of use, is no longer effective lowering
calcium (tachyphylaxis)
Usual doses of calcitonin are 28 U/kg of body weight
IV, SC, or IM every 612 hours

Glucocorticoids
increase urinary calcium excretion and decrease
intestinal calcium absorption when given in
pharmacologic doses, but they also cause negative
skeletal calcium balance
Effective:
Malignancy
Vitamin D intoxication
Autoimmune diseases that mimic FHH

Dialysis
Treatment of choice for severe hypercalcemia
complicated by renal failure, which is difficult to
manage medically
Peritoneal dialysis with calcium-free dialysis fluid can
remove 512.5 mmol (200500 mg) of calcium in 2448
hours and lower the serum calcium concentration by
0.73 mmol/L (312 mg/dL).

Phosphate therapy
The usual oral treatment is 11.5 g phosphorus per day
for several days, given in divided doses
Intravenous phosphate
one of the most dramatically effective treatments
toxic and even dangerous (fatal hypocalcemia)
It is used rarely
severely hypercalcemic patients with cardiac or renal
failure

Thank you!