What Causes Hypercalcemia?

Patient Presentation
A 19-month-old male was referred to a regional children’s hospital for mild hypercalcemia that was noted when routine laboratories were drawn in an emergency room when he presented with bronchiolitis. He was otherwise well with normal growth parameters and development. The parents denied any medication, vitamins or herbal use including topical medications. There was some blood pressure medication and oral contraceptives in the parents and grandparents homes but the family denied that the child had access to the medications. He had been well with no fatigue, nervousness, changes in skin, hair, sleep or weight. A record review from the emergency room showed a normal saline bolus and albuterol were given but no calcium. The family history had no cancers, bone, kidney, or hearing problems.

The pertinent physical exam showed a mildly tachypneic male with otherwise normal vital signs and growth parameters in the 10-50% range. Pulse oximeter was 90% on room air. HEENT showed mild rhinorrhea with wet mucosa. Thyroid was normal. Lungs were coarse with mild end expiratory wheezing. There was normal skin except for mild shin bruising bilaterally. The laboratory evaluation at the outside hospital found normal electrolyes, BUN, creatinine, phosphorus, magnesium, albumin, T4, TSH, and parathyroid hormone. His ionized calcium was 5.73 mg/dL (normal up to 5.52), 25-OH Vitamin D was normal and spot urine calcium/creatinine ratio was .65 (normal up to .6 for age). Chest radiograph showed mild hyperexpansion with patchy areas of atelectesis. The diagnosis of bronchiolitis and idiopathic hypercalcemia were found. As there was no obvious malignancy, parathyroid hormone or Vitamin D abnormalities, and the patient was asymptomatic, it was felt that this was most consistent with a transient abnormality or familial hypercalciuric hypercalcemia. A pediatric endocrinologist recommended to recheck both 1,25-OH Vitamin D, and an ionized calcium in 1-2 weeks. If these were abnormal then additional studies may be indicated. At 2 weeks, the repeat lab tests were normal on the infant, but the mother had a spot calcium/creatinine ratio which was elevated, and the mother was now being evaluated further.

Discussion
Calcium homeostasis is regulated by mechanisms involving the absorption from the gastrointestinal tract, bone deposition and resorption, and renal excretion. To review Vitamin D homeostasis click here.

Serum calcium is found in three forms: free (47%), protein bound (43%) and diffusable calcium complexes (10%). The protein binding proteins are albumin (80%) and globulin (20%). The free calcium is the most important biologically. Acidosis also increases free calcium and alkalosis decreases free calcium.

Problems associated with hypercalcemia include nausea, emesis, abdominal pain, constipation, polyuria, dehydration, mental status changes and coma.

Learning Point
The differential diagnosis of hypercalcemia includes:

  • Hyperparathyroidism
    • Primary
    • Familial isolated
    • Familial hypercalciuria hypercalcemia
    • MEN I and II
  • Vitamin D excess
    • Chronic granulomatous disorders
  • Drugs
    • Catecholamines
    • Lithium
    • Teriparatide
    • Theophylline
    • Thiazides
    • Vitamin A excess
  • Malignancies
    • Ectopic PTH-producing tumors
    • Pheochromocytoma
  • Other
    • Acromegaly
    • Aluminum excess
    • Adrenal insufficiency
    • Hypophosphatemia
    • Hyperthyroidism
    • Immobilization
    • Idiopathic infantile hypercalcemia
    • Milk alkali syndrome
    • Parenteral nutrition
    • Renal failure
    • Williams syndrome

Questions for Further Discussion
1. What are treatments for hypercalcemia?
2. What is included in the differential diagnosis of hypocalcemia?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: fluid and Electrolyte Balance and Calcium.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Bakerman’s ABC’s of Interpretative Laboratory Data. Fourth Edit. Interpretative Laboratory Data Inc. Scottsdale, AZ. 2002;123-125.

Rudolph CD, et.al. Rudolph’s Pediatrics. 21st edit. McGraw-Hill, New York, NY. 2003:163-64,2152-56.

Shane E. Diagnostic Approach to Hypercalcemia. UptoDate.
Available from the Internet at http://www.uptodate.com/contents/diagnostic-approach-to-hypercalcemia?source=search_result&search=diagnostic+approach+to+hypercalcemia&selectedTitle=1%7E150 (rev. 1/25/2013, cited 2/8/13).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Systems Based Practice
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

  • What Can I Do To Help With Sibling Rivalry?

    Patient Presentation
    A 3-year-old male came to clinic for his health supervision visit. The mother described that the 3-year-old was always bothering his 5-year-old brother and they would have lots of verbal fights which were becoming more physical. The mother says a typical situation was one where the 3-year-old wanted to play with his brother, but the brother was doing something else. He usually tried to convince his brother to play, then slowly moved into the 5-year-olds personal space, then took the 5-year-old’s possessions. The 5-year-old’s usual response was to ignore the brother’s negotiating, verbally warn the brother to leave his space, and then yell loudly for a parent or hit the brother when the possessions were taken. The mother wasn’t sure what to do and was worried because the 3-year-old seemed to be getting more aggressive. The social history was negative including mental illness and domestic violence.

    The pertinent physical exam showed a healthy male with growth parameters in the 10-50%. His examination was normal. The diagnosis of normal sibling rivalry but with recent escalation was made. The mother was counseled in understanding that it is normal for the younger sibling to want to play with the older sibling but both have different developmental needs with the 3-year-old just learning cooperative play and the 5-year-old’s being very good at it. The mother was encouraged to help the older son find ways they could play together (“You play with the horses and I’ll play with the other animals on the farm”), to continue to ignore when appropriate and to walk away or find an adult when needed to help with the conflict. For the younger child, she was encouraged to monitor him and to redirect him earlier in the process if possible. For example, once the 3-year-old starts to enter the 5-year-olds physical space she could verbally redirect him to another activity in the same area. Also helping both children understand their physical boundaries and possessions, such as “Those are your brother’s toys and he is playing with them now. You can play with your toys.”

    Discussion
    Sibling rivalry is a common problem. It often occurs around the time of birth of a second child. There can be aggression towards the sibling and/or developmental regression in the child.
    Older children can “…regularly wage war, physically and psychologically, within the home.” While this can worry and irritate parents, the inter-sibling confrontations also offer the opportunity to learn conflict resolution, adaption, sharing and can also evolve the relationship “…into one of extraordinary closeness and depth.”

    Factors that can help in understanding the problem include:

    • Temperament – how does the child react in general to the world
    • Development – what is the child’s cognitive understanding of the world
    • Parental favoritism/descriptions of the child – while there may not be overt favoritism, the words a parents uses to describe a child are important including typecasting or stereotyping. There may also be special needs that a sibling necessarily has that must be met by the parents and therefore are seen as favoritism such as a child with special health care needs.
    • Perception – how the child views the other sibling(s) and parents
    • Privacy – is there private space for the child to go, to store belongings or to have private time with parents?
    • Analysis of typical fights – a “blow-by-blow” description of the last event may bring insight into provocations, conflict resolution strategies used, parental interventions, etc. which may identify typical enhancing and mitigating factors in the conflicts.

    Learning Point
    Help for sibling rivalry includes:

    • Encourage parental understanding of the situation
    • Encourage child understanding of the situation – having children begin to understand that fair is not necessarily equal in a family as everyone needs something different
    • Teach conflict resolution – including sharing and taking turns, ignoring the behavior, talking it out, walking away from the situation, or getting an adult (or someone else) to help are excellent strategies.
    • Parental modeling of what they would like the child to do is powerful. Advising parents to talk and not hit (e.g. talk it out) or to put themselves in time out (e.g. walking away).
    • It is also helpful for a parent to tell the child what behaviors are appropriate. For example it is okay to be angry with their sibling and they could hit a pillow or bounce a ball, but not hit the sibling or throw the pillow or ball at the sibling.
    • Praise that is truthful – Praise for behavior that the parent wants to encourage can be good. “I thought the way you ignored your sister who kept asking you about XXX was good. She finally got bored and walked away.”

    For most families these treatments can help them through many sibling rivalry conflicts. However, there are many situations that persist beyond the normal time frame, or are intensified beyond the normal circumstances. For example, a 2 year old who bites a younger sibling once would probably be considered normal sibling rivalry. But a 10 year old who continually bites a sibling probably is not. This may be a child who is physically abusing his or her sibling and is perpetrating sibling violence. Sibling violence can be physical, psychological, emotional or sexual, as is other types of domestic violence. Many health care providers and family members do not recognize such acts as sibling violence because they are perpetrated between children and youth. But if perpetrated between adults such acts would be considered illegal. Such acts are often dismissed as “just being kids,” “roughhousing,” or “boys will be boys.” Behavioral and psychological treatment is needed to help these children and families and stop the violence.

    Questions for Further Discussion
    1. What history questions would help you to determine if interpersonal conflict is normal sibling rivalry or sibling violence?
    2. What local resources are available to help treat sibling violence?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Family Issues.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    Phillips DA, Phillips KH, Grupp K, Trigg LJ. Sibling Violence Silenced, Rivalry, Competition, Wrestling, Playing, Roughhousing, Benign. Advances in Nursing Science. 2009:32;e1-e16.

    Needlman A. Sibling Rivalry in Behavioral and Developmental Pediatrics. Park and Zuckerman eds. Little Brown and Co. Boston, MA. 1995:384-86.

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

  • What Else Looks Like Atopic Dermatitis?

    Patient Presentation
    A 13 month-old female came to clinic with dry itchy skin that has been worsening over 3 days. The mother noticed that it is worse on her arms, legs and face, and she has had dry skin before that she treated with some lotion occasionally. She has been scratching quite a bit and the areas are becoming redder. The family history shows that mother has dry skin also.

    The pertinent physical exam reveals a healthy female with generalized dry skin that is mainly papular and red. Excoriation is seen on the cheeks, behind the ears, and in the flexural areas of the elbows and knees. These areas are also more pink-red in color than the surrounding skin. There are no areas that appear infected. The diagnosis of atopic dermatitis was made. Her mother was educated as to the natural history of the disease. She was told to use “thick” emollients such as petrolatum to protect her skin and use them every couple of hours to keep her skin moist. She was also told to use thinner emollients, such as a cream or lotion, if she was going to be in a warm place so she wouldn’t sweat under the emollients and irritate her skin. After bathing with a mild “beauty bar” such as Dove® or a non-soap alternative such as Cetaphil® she could pat her dry and apply the emollients.

    Discussion
    Atopic dermatitis or eczema is a common dermatological skin problem which characteristically is a pruritic, papular eruption with erythema. Like most papulosquamous eruptions it often occurs in intertrigenous areas in people with allergic constitutions or with a family history of atopy. It does not have scale which occur in other papulosquamous eruptions such as psoriasis or tinea. Sometimes atopic dermatitis is described as the “itch that rashes.” Rubbing and scratching can lead to excoriation and, over time, lichenification. There can also be secondary infections or changes to the skin pigmentation (hyper- or hypo-) in affected areas. Emollients for skin rehydration are a mainstay of treatment. Topical steroids are commonly used to decrease inflammation in affected areas. Immunosuppressants such as tacrolimus are also used in some cases.

    Complications includes secondary bacterial infections with Group A Beta-hemolytic Streptococcus or Staphlococcal species. Oral or intravenous treatment of bacterial infections is common with appropriate agents. Eczema herpeticum is another complication which has an umbilicated appearance of papular, vesicular and pustular lesions. Luckily, eczema vaccinatum (caused by smallpox virus) does not occur anymore because of no circulating virus in most parts of the world.

    Learning Point
    The differential diagnosis of atopic dermatitis includes:

    • Xeroderma
      • Variants include
        • Dishydrotic eczema
        • Ichthyosis vulgaris
        • Keratosis pilaris
        • Nummular eczema
        • Perioral dermatitis
        • Pitaryiasis alba
    • Contact dermatitis
      • Allergic- papular or papulovesicular that is pruritic
      • Irritant contact dermatitis – usually milder, less pruritic, often seen on cheeks/chin because of saliva or areas that are rubbed
    • Seborrheic dermatitis – greasy yellow or pink-colored scale with little pruritis. See also this case.
    • Scabies – highly pruritic, may or may not see linear burrows. See also this case.
    • Tinea corporis – pink papular round lesions with small scale on the edge
    • Acrodermatitis enteropathica – papular, vesicular and bullous lesions, has failure to thrive, alopecia, diarrhea and nail changes, associated with zinc deficiency
    • Drug eruptions
    • Histiocytosis
    • Ichythiosis and other keratin disorders
    • Impetigo
    • Lymphoma, cutaneous
    • Phenylketonuria – usually diagnosed because of screening, but may have diffuse hypopigmentation, eczema, photosensitivity as dermatological changes.
    • Psoriasis – more on extensor surfaces with mica-like scale, has delinated border
    • Wiskott-Aldrich syndrome – X-linked recessive, severe eczema with thrombocytopenic purpura and immune deficiencies

    Questions for Further Discussion
    1. What is the difference between atopic dermatitis and ichythosis?
    2. How have immunomodulators changed the treatment of atopic dermatitis?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Eczema

    To view current news articles on this topic check Google News.

    To view images related to this topic check <a href="To view current news articles on this topic check Google Images.

    “>Google Images.

    Krakowski AC, Eichenfield LF, Dohil MA. Management of atopic dermatitis in the pediatric population. Pediatrics. 2008 Oct;122(4):812-24.

    Hebert AA. Atopic Dermatitis. ePocrates.
    Available from the Internet at https://online.epocrates.com/u/293587/A. (rev. 1/18/2013, cited 1/28/13).

    ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    8. Health care services aimed at preventing health problems or maintaining health are provided.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

    Author

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital