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Humoral hypercalcemic crisis in a pregnant woman with uterine leiomyoma.
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PMID:  22416164     Owner:  NLM     Status:  PubMed-not-MEDLINE    
We report a case of parathyroid hormone-related protein-mediated hypercalcemic crisis in a 36-year-old pregnant woman, who was admitted to women hospital with recurrent vomiting and epigastric pain. She was diagnosed with uterine fibroid since the first month of her pregnancy, but the pregnancy had been uneventful. Serum calcium was 4.8 mmol/l, while parathyroid hormone was low. Hypercalcemia was attributed to humoral hypercalcemia associated with uterine fibroid as other causes of hypercalcemia were excluded.
Ali Rahil; Fahmi Yousef Khan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of emergencies, trauma, and shock     Volume:  5     ISSN:  0974-519X     ISO Abbreviation:  J Emerg Trauma Shock     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-03-14     Completed Date:  2012-08-23     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101493921     Medline TA:  J Emerg Trauma Shock     Country:  India    
Other Details:
Languages:  eng     Pagination:  87-9     Citation Subset:  -    
Department of Medicine, Hamad General Hospital, Doha, Qatar.
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Journal Information
Journal ID (nlm-ta): J Emerg Trauma Shock
Journal ID (publisher-id): JETS
ISSN: 0974-2700
ISSN: 0974-519X
Publisher: Medknow Publications & Media Pvt Ltd, India
Article Information
Copyright: © Journal of Emergencies, Trauma, and Shock
Received Day: 08 Month: 1 Year: 2011
Accepted Day: 04 Month: 10 Year: 2011
Print publication date: Season: Jan-Mar Year: 2012
Volume: 5 Issue: 1
First Page: 87 Last Page: 89
ID: 3299164
PubMed Id: 22416164
Publisher Id: JETS-5-87
DOI: 10.4103/0974-2700.93093

Humoral hypercalcemic crisis in a pregnant woman with uterine leiomyoma
Ali Rahilaff1
Fahmi Yousef Khanaff1
Department of Medicine, Hamad General Hospital, Doha, Qatar
Correspondence: Address for correspondence: Dr. Fahmi Yousef Khan, E-mail:


Severe hypercalcemia during pregnancy is a rare but potentially life-threatening condition that poses a significant danger to mother and baby;[1, 2] in general, hypercalcemia during pregnancy may arise from several different pathological conditions. The most common etiology is primary hyperparathyroidism. Other causes include hyperthyroidism, immobilization, vitamin D, and vitamin A overdose, familial hypocalciuric hypercalcemia, diuretic phase of acute renal failure, chronic renal failure, thiazide diuretics, sarcoidosis or other granulomatous diseases, milk-alkali syndrome, and Addison's disease.[2] Although rare, hypercalcemia may also develop in pregnant women due to parathyroid hormone-related protein (PTH-rP) producing malignant tumors (humoral hypercalcemia of malignancy). Hypercalcemia due to high serum levels of PTH-rP in the setting of benign disease is extremely rare. We report a 36-year-old pregnant woman with uterine fibroid who developed hypercalcemic crisis at her third trimester.


A 36-year-old Kenyan woman, primigravida at 34-week spontaneous pregnancy, admitted to women hospital on April 12, 2008, with recurrent vomiting and epigastric pain. She was diagnosed with uterine fibroid since the first month of her pregnancy, but the pregnancy had been uneventful. She had history of weight loss (10 kg), no change in bowel habits, no hematemesis or rectal bleeding, and no history of hematuria or passing stones. The patient was using iron tablets; otherwise her medical history was unremarkable. On examination, she looked ill, markedly dehydrated, and drowsy. Her blood pressure was 126/76 mmHg, pulse rate 94 min–1, respiratory rate 30 min–1, and temperature 36.6°C; she had no lymphadenopathy, no thyromegaly, and no edema. Abdominal examination showed a uterus size of 40 weeks and tender epigastric area. Neurological examination showed a drowsy and hypotonic lady with brisk deep tendon reflexes. There was no obvious focal neurological sign. Planter reflexes were down-going. Chest and cardiovascular systems were unremarkable.

The findings of initial investigations were as follows: hemoglobin (Hb) 8.7 g/dl, WBCs 7000 μl–1, platelets 445 000 μl–1; and ESR 109 mm/h. Peripheral blood smear showed toxic granulation of WBCs. Blood chemistry: BUN 4.4 mmol/l, creatinine 59 μmol/l, HCO3 22 mmol/l, Na 138 mmol/l, Ca 4.8 mmol/l (normal: 2.1-2.6), uric acid 508 μmol/l, lactic acid 1.2 mmol/l, and phosphorous 0.8 mmol/l. HIV serology was negative. A retrospective measurement of calcium at 14 weeks’ gestation was obtained at 2.43 mmol/l. Liver function test: ALT 4 u/l, AST 11 u/l, ALP 150 u/l, total protein 72 g/l, and albumen 30 g/l. Lipid profile: cholesterol 4.05 mmol/l and triglyceride 3.59 mmol/l. Hormone study: PTH 3 pg/ml (normal:15-65), TSH 0.68 mIU/l (normal: 0.45-4.5), free thyroxin 16.6 pmol/l (normal: 9-20), cortisol 1849 nmol/l, and vitamin D 15 ng/ml (normal: 30-80). Serum protein electrophoresis as well as serum level of angiotensin-converting enzyme were normal.

In consultation with the internist, the patient was given normal saline infusion at 250 ml/h with close monitoring of her urine output plus intramuscular calcitonin, and she was transferred to the medical intensive care unit.

Based on these laboratory findings, the possible diagnosis was humoral hypercalcemia of benignancy (uterine fibroid). PTH-rP is the primary mediator that causes hypercalcemia. However, we did not check for the PTH-rP level because of lack of facilities.

In the intensive care unit, the patient developed rupture membrane, which entailed urgent cesarean section while calcium remained high. However, because of hypercalcemia and reduction in the urine output with a rise in serum creatinine, the nephrologist was consulted for urgent hemodialysis before the operation. The surgery was complicated by bleeding, leading to hypotension requiring blood transfusion despite the successful delivery of a baby girl weighing 2.9 kg and removal of uterine masses measuring in aggregate 30 × 25 × 15 cm, which were submitted to a histopathological examination and the histopathology report was consistent with leiomyoma with calcifications but no evidence of malignancy. The postoperative clinical course was further complicated by septicemia and septic shock, which required vasopressors and broad-spectrum antibiotics.

Postoperative laboratory test results were as follows: serum calcium 2.34 mmol/l, phosphorus 1.1 mmol/l, BUN 6.2 mmol/l, Cr 75 mmol/l, Na 143 mmol/l, K 4.2 mmol/l, HCO3 16 mEq/l, chloride 113 mEq/l, albumin 21 g/l, serum lactate 5.19, serum PTH 155 pg/ml, serum amylase 88 u/l, serum lipase 73 u/l; Hb 5.8 g/dl, platelets 125 000 μl1. The CT scan of the chest and pelvis showed no evidence of mass lesion or organomegaly. MRI of the brain that was done because of the deterioration in the level of consciousness showed evidence of infarcts involving the right cerebellum, the lentiform nucleus on both sides, as well as the cortical regions in frontal, parietal, and occipital lobes. MRA revealed evidence of vasospasm of the internal carotid, the middle and the anterior carotid arteries; the findings are suggestive of diffuse ischemic changes secondary to hypoxic insult. Subsequently, her condition began to improve but her neurological status required extensive physiotherapy for the generalized muscle weakness and stiffness. The patient was discharged home, with a final diagnosis of humoral hypercalcemia associated with a uterine fibroid. Serum calcium remained within the normal range over the subsequent 6 months [Figure 1].


PTH-rP was discovered in 1987 by Mosley et al as a tumor-derived factor that caused humoral hypercalcemia of malignancy. Breast, lung, ovarian, renal cell carcinomas, lymphoma, and multiple myeloma are the malignancies that are most commonly associated with humoral hypercalcemia. Although extremely rare, hypercalcemias due to high serum levels of PTH-rP in the setting of benign disease (humoral hypercalcemia of benignancy) have been reported.[1, 38]

PTH-rP has been identified in the normal tissue of the reproductive tract. It is thought to be important during late pregnancy and lactation. The exact function is unknown, but it has been postulated that it may cause vasodilatation and smooth muscle relaxation and may be involved in the rhythmicity of myometrial contractions before parturition.

In our patient, although PTH-rP was not assessed due to lack of facilities, hypercalcemia was attributed to humoral hypercalcemia associated with a uterine fibroid, since other causes of hypercalcemia such as primary hyperparathyroidism, vitamin A and D intoxication, sarcoidosis, multiple myeloma, milk-alkali syndrome, adrenal insufficiency, and immobilization were excluded on the basis of laboratory and clinical data.

Our patient had low level of PTH, which was attributed to suppression of secretion by increased levels of serum calcium, whereas postoperative PTH was high, reflecting rebound hyperparathyroidism due to rapid normalization of calcium level by hemodialysis.

The most common symptoms of hypercalcemia are weakness, fatigue, nausea, vomiting, anorexia, and headaches.[2] On the other hand, the patient in hypercalcemic crisis defined as serum calcium levels above 3.5 mmol/l may present with anorexia, protracted vomiting, depression, proximal muscle weakness, constipation, osteopenia, confusion, hypertension, nephrolithiasis, pancreatitis, and coma.[2] Our patient was in hypercalcemic crisis and presented with recurrent vomiting and epigastric pain.

The treatment of hypercalcemia depends on the level, the chronicity, and the underlying cause of the problem. Hypercalcemic crisis in pregnancy is a potentially life-threatening condition that needs prompt intervention. The main aspects of treatment include adequate hydration and correction of electrolyte abnormalities. Pharmacologic agents to treat hypercalcemia have not been adequately studied in pregnancy. Calcitonin does not cross the placenta and has been used safely. Oral phosphate has also been used but is limited by diarrhea, hypokalemia, and risk of soft tissue calcifications. Bisphosphonates and mithramycin are contraindicated because of their adverse effects on fetal development. Our patient needed urgent cesarean section; therefore, hemodialysis was carried out to treat hypercalcemia.


Humoral hypercalcemia is a well-recognized complication of uterine fibroid that should be considered in differential diagnosis of hypercalcemia in a pregnant woman who had a uterine fibroid.


Source of Support: Nil.

Conflict of Interest: None declared.

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[Figure ID: F1]
Figure 1 

Calcium level during pregnancy, after delivery, and 6 months after delivery

Article Categories:
  • Case Report

Keywords: Humoral hypercalcemia, hypercalcemic crisis, uterine fibroid.

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