Table 3 Endocrine Management of patients with Prader-Willi syndrome

Birth to 3 months or at diagnosis

Diagnosis

• DNA methylation analysis as initial test

• Subsequent determination of genetic subtype

Hypothyroidism

• TSH, FT4

• Start treatment if hypothyroxinemic

Growth Hormone

• Initiate discussion of hGH therapy

3 months through childhood

Hyperphagia

• Provide education on: nutritional phases, need for food security, strict dietary control and routine, regular physical

• Nutrition referral

Cryptorchidism

• Urology referral

• Consider trial of hCG

Hypothyroidism

• Annual TSH and FT4 starting at age 1

Growth Hormone

• Consider starting therapy in the first few months of life, or prior to onset of obesity.

• No pre-treatment testing required.

• Starting dose: 0.5 mg/m2/day with progressive increase to 1 mg/m2/day.

• Aim to keep IGF-1 levels between +1 and +2 SDS

Growth Hormone Monitoring

Prior to starting therapy:

1. Otolaryngology referral if there is a history of sleep disordered breathing, snoring, or enlarged tonsils or adenoids are present, with consideration of tonsillectomy and adenoidectomy

2. Referral to a pulmonologist or sleep clinic

3. Sleep oximetry in all patients, preferably polysomnographic evaluation

4. Spine film with orthopedic referral if significant scoliosis present

5. Bone age film if at appropriate chronologic age

6. Consider body composition evaluation (e.g. DXA)

Contraindications to therapy:

1.Untreated severe OSA

2.Uncontrolled diabetes

3.Severe obesity

4.Active malignancy

5.Active psychosis

While on therapy:

1. IGF-1 every 6–12 months

2. Repeat polysomnography within the first 3–6 months of initiating hGH therapy

3. Spine film and/or orthopedic assessment if concerns for scoliosis progression

Adrenal insufficiency

• Consider obtaining cortisol and ACTH levels during acute illness or other stressful situation to clarify diagnosis

• Consider stress dose steroids for all patients with PWS during stress, to include mild upper respiratory infections and the perioperative period

Puberty through adulthood

Hypogonadism

• Sex steroid therapy as needed to promote normal timing and progression of puberty in males and females

• Adult females: sex steroid replacement if oligo/amenorrhea or low BMD in the setting of a low estradiol level

• Adult males: testosterone replacement as for hypogonadal males. May be behavioral benefits from topical androgen formulations

Growth Hormone

• Adults: evaluate the GH/IGF-1 axis prior to initiating hGH

• Adult staring dose: 0.1-0.2 mg/day

• Aim to keep IGF-1 0 to +1 SDS

Diabetes

• Screen prior to initiation of and annually during growth hormone therapy in patients ≥ 12 years of age

• Screen in obese individuals as is recommended for the general population

Obesity

Periodic monitoring of/for:

1. Lipid profiles

2. Hepatic steatosis