Tricky cases - Hypercalcemia

A 52 years old teacher was brought to hospital by her relatives with a history of abnormal behaviour. She was apparently well until 3 weeks back, when she became increasingly forgetful. Over the next week she became over talkative and aggressive.

She was seen by a psychiatrist in the private sector and was started on treatment for bipolar affective disorder. A CT scan of the brain, TSH and basic investigations were normal.

Despite initial treatment her symptoms got worse. At the time of admission she was restless and agitated. Her hemodynamic parameters and neurological examination was normal.

What non-psychiatric condition should be considered in a patient presenting with psychiatric manifestations?

• Electrolyte abnormalities/ hyper/hypoglycemia
• Endocrine diseases
• Cushing syndrome
• Thyroid disorders
• Central nervous system causes
• Infections
• Tumors
• Autoimmune encephalitis
• Vasculitis
• Drugs and toxins
• Alcohol!

Upon the suspicion of encephalitis LP and EEG were planned and empirical treatment was started.

On further questioning her daughter came out with the information that she noted her mother used to go to toilet to pass urine about 3-4 times every night.



What are the causes for polyuria?

• Sometimes, frequency can be misinterpreted as polyuria.
• Prostate diseases in men
• Overactive bladder in women
• Urinary tract infections
• When there is true polyuria, consider
• Diabetes mellitus
• Diabetes insipidus
• Central
• Nephrogenic
• Psychogenic polydipsia

Urgent S. Ca was sent. Within few hours department of biochemistry informed the ward that the patients Ca level was unmeasurably high! On repeated testing the value had come as 5mmol/l !! Serum ionized calcium level was more than twice the upper limit of normal.



Now what??

• First priority is to correct hypercalcemia as it can cause life threatening complications

How are you going to manage severe hypercalcemia?

• Advice patient to limit high calcium food and beverages. Stop calcium/ Vit D supplements if she is on any.
• Volume expansion
• Give large volumes of isotonic saline (initially up to 200-300ml/hr) to maintain urine output around 100ml/hr.
• Bisphosphonates
• IV pamidronate (60mg over 2 hours) or IV zoledronic acid (4mg over 20min)
• Takes minimum of 2-3 days to act.
• Loop diuretics
• IV furosemide is not recommended unless in the presence of heart failure.
• However, in practice many clinicians still use furosemide.
• Steroids
• IV hydrocortisone is effective if hypercalcemia is due to malignancies or granulomatous diseases.
• However, this also is used by clinicians until the diagnosis is established.
• Treat the cause!

What are the common causes for hypercalcemia?

• There are more than 30 causes for hypercalcemia. Let's list a few common causes.
• Excess PTH - Hyperparathyroidism
• Parathyroid adenoma/ Carcinoma
• Parathyroid hyperplasia
• Malignancies can produce hypercalcemia in several ways
• PTH related peptide
• Many malignancies can secrete this causing hypercalcemia
• Lytic bone metastasis
• Granulomatous diseases causing excess vit D
• Sarcoidosis
• TB
• Drugs
• Read about the other causes for hypercalcemia

How are you going to identify the etiology?

The list of investigations is long. However, two tests can usually guide you to the correct pathway.

• Phosphate level
• Low or low normal if the cause is PTH/ PTHrP mediated
• PTH level
• In hypercalcemia PTH value should be undetectable.
• EVEN A NORMAL VALUE INDICATES PTH MEDIATED DISEASE (HYPERPARATHYROIDISM)

PTH value of the patient was more than 700pg/ml (10-65). The diagnosis of HYPERPARATHYROIDISM was made.

This patient was also started on Saline rehydration, Zoledronic acid, Furosemide and IV hydrocortisone. Even after 2 days of treatment her calcium was still above normal.

What other treatment options are available?

• Calcitonin and Denosumab
• Not freely available in SL
• Cinacalcet
• A calcimimetic agent which inhibits PTH secretion.
• Renal replacement
• Especially if the patient has life threatening complications or renal failure.

Cinacalcet 30mg bd was started. With that her calcium levels normalized within a few days.

Localization of abnormal parathyroid

• Patients with hyperparathyroidism need removal of the abnormal gland.
• Not all. There are specific indications. You may read if interested.
• Before removal the abnormal gland/glands should be localized.
• Helpful investigations include
• USS neck
• CT neck
• Tc 99m Sestamibi scan is one of the most useful investigations. 
• Tracer get retained in the abnormal tissues.
• This can be combined with novel CT techniques to obtain more information. (SPECT)

Patient was subjected to a Tc99m Sestamibi scan.

Retained tracer noted in the left inferior gland.

Patient underwent a successful parathyroidectomy and the intraoperative PTH level normalized within few minutes.

HOMEWORK

• Read about the clinical manifestations of hypercalcemia.

PICTURE CHALLENGE

Identify these abnormalities in a patient diagnosed to have primary hyperparathyroidism.

1. 

2.