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FD & MAS DIAGNOSIS AND TREATMENT GUIDELINES

The following are set of recommendations for the diagnosis, treatment, and follow-up of patients with FD and/or MAS. They are somewhat technical and it may be useful to discuss them with your doctor. Detailed explanations for these recommendations may be found in the chapters on FD/MAS on the Orphanet web site [INSERT LINK] or in the chapter in the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism [INSERT LINK].

RECOMMENDATIONS FOR ENDOCRINE FOLLOW-UP OF PATIENTS WITH FD/MAS

1.

Pituitary: Growth hormone (GH) and prolactin (PRL) excess are common in MAS (20%). The signs and symptoms can be very subtle. GH excess can worsen craniofacial (CF) bone disease.

 

a.

all patients should have an oral glucose tolerance test (OGTT) to assess for non-suppressible GH at least once (GH > 2.0 ng/ml at 60 min on standard OGTT is diagnostic).

b.

non-suppressible GH with elevated insulin-like growth factor-1 (IGF-1) should be treated

c.

what to do with non-suppressible GH and normal IGF-1 is not clear (these patients will have an abnormal overnight GH secretion pattern)

 

 

2.

Thyroid: Hyperthyroidism is common.

 

a.

Check thyroid function tests (TSH, FT4, T3, T4). T3 dominant hyperthyroidism is most common, 40%)

b.

Treat with an oral anti-thyroidal (methimazole, PTU)

c.

If definitive treatment is needed, we recommend surgery not radioiodine (thyroid cancer in MAS is rare, and radioiodine could be an additional risk factor beyond the Gs mutation).

d.

Annual ultrasound of the thyroid to follow lesions and biopsy clearly dominant, large or changing lesions.

 

 

3.

Parathyroid: Primary hyperparathyroidism is rare, secondary (to vitamin D deficiency) is common.

 

a.

Check ionized calcium or total calcium and PTH annually.

 

 

4.

Adrenal: Cushings in the neonatal period occurs, but has not been reported past the first year. Some cases of neonatal Cushings resolve spontaneously.

 

a.

Check adrenal reserve in resolved cases of neonatal Cushings.

 

 

5.

Renal: Phosphate wasting with or without hypophosphatemia, and/or rickets/osteomalacia is common (40%).

 

a.

Check serum phosphate and renal phosphate handling (second AM void or 24 hour urine for TMP/GFR).

b.

Treat frankly low or low-normal serum phosphate with low TMP/GFR

c.

See separate treatment algorithm.

 

 

6.

Gonads: Precocious puberty (PP) in girls is common, PP in boys is less common, small testicular masses of leydig cell hyperplasia are common.

 

a.

Treat PP in girls with an aromatase inhibitor (preferred), or tamoxifen.

b.

Treat PP in boys with an aromatase inhibitor and an anti-androgen.

c.

Check for and treat secondary central PP in children with PP with a long-acting GnRH agonist.

d.

Check for Leydig cell masses in men with screening testicular ultrasounds suspicious masses should undergo excisional biopsy to exclude cancer.

 

RECOMMENDATIONS FOR FOLLOW-UP OF PATIENTS WITH FD/MAS

1.

Craniofacial: very common, especially skull base, vision loss is uncommon, hearing loss even more uncommon, sarcomatous degeneration is rare, while axial and appendicular FD quiets with age, CF probably continues to slowly progress.

 

a.

Find a craniofacial and neurosurgical team experienced in treating CF FD!

b.

Avoid surgery in the absence of visual or hearing impairment. (nerves may be surrounded by and unaffected by FD bone for decades).

c.

Severe pain or sever disfigurement may be an indication for surgery as well.

d.

Annual vision testing by a neuro-ophthalmologist and annual hearing testing are recommended.

e.

Annual CT of skull and mandible are recommended.

f.

Screen for and treat all endocrinopathies which adversely affect bone.

g.

Little evidence that bisphosphonates are effective in CF FD (even for pain).

h.

Bone scan at baseline and at some interval (?every few years).

 

 

2.

Axial and Appendicular skeleton: very common, fractures frequent (esp. before 15 y.o.), shepherd's crook deformity common, pain common, sarcomatous degeneration (cancer) rare.

 

a.

Find an orthopedic surgeon experienced with FD!

b.

In general, less is better in the surgical treatment of FD.

c.

Bracing may be helpful?

d.

Screen for and treat all endocrinopathies which adversely affect bone.

e.

Bone scan at baseline and at some interval (?every few years).

f.

Bisphosphonates can decrease pain and markers of bone turnover, probably no effect on course of disease or fracture rate.

g.

Maintaining strength is important, swimming is an excellent exercise, cycling is good also

 

RECOMMENDATIONS FOR TREATMENT OF RICKETS/ OSTEOMALACIA/ HYPOPHOSPHATEMIA

1.

Goal: Serum phosphorus in the age-appropriate normal range

 

 

2.

Treatment:

 

a.

Phosphorus: 15-60 mg/kg/day (1-3 g/day adults), divided, 4-5 times per day Phosphorus treatment usually causes secondary hyperparathyroidism, so 1,25 vitamin D (calcitriol) is usually added to prevent this.

b.

Treatment with calcitriol not only prevents secondary hyperparathyroidism but may also increases GI phosphorus absorption, improve bone healing (especially at high doses, and improve renal tubular maximum for phosphate reabsorption (i.e. increase TmP/GFR).

c.

Calcitriol: approximately 30 ng/kg/day (1.5 µg/day, (six 0.25 µg pills/day) for a 70 kg man), range15-60 ng/kg/d (three-twelve 0.25 µg pills/day)

 

 

3.

Possible Complications:

 

a.

Hypercalciuria (high urine calcium). With kidney stones (nephrolithiasis) or kidney calcification (nephrocalcinosis) and decreased kidney function.

b.

Hypercalcemia (high blood calcium). Less common than hypercalciuria.

c.

GI upset. Due to the phosphate. Dividing the doses over 4-5 times per day and with food helps.

 

 

4.

Follow-up:

 

a.

Baseline ultrasound of the kidneys to rule out nephrolithiasis or nephrocalcinosis (which some patients are at risk for at the outset).

b.

Every 3 month urine test (second A M void) for calcium (Ca) and creatinine (Cr), if Ca/Cr >= 0.20, check urine for blood, if presnt, decrease calcitriol, and obtain 24 hour urine for calcium and creatinine with the goal to keep urinary calcium in the normal range. If it is high, decrease calcitriol again. If Ca/Cr <= 0.20 and serum phos and PTH ok, maintain regimen (pediatric urinary calcium: Ca/Cr upper limit: < 7mo 0.86, 7-18 mo 0.6, 19 mo – 6 y 0.42: 24 hr urine: < 4mg/kg/24hr).

c.

Every 3 month serum calcium, phosphorus, and PTH.

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