Clinical Guideline

ADRENARCHE

MANAGEMENT OF CHILDREN PRESENTING WITH SIGNS OF EARLY ONSET /BODY ODOUR/

Includes guidance for the distinction between adrenarche, precocious and other abnormalities of secondary sexual development

Date of First Issue 24 / 03 / 2015 Approved Current Issue Date 24 / 03 / 2015 Review Date 24 / 03 / 2018 Version 1.0

Author / Contact Sarah Kiff / Louise Bath Group Committee – SPEG MCN Protocols Group Final Approval SPEG MCN Steering Group

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Management of Adrenarche in children: presenting with signs of early onset pubic hair/body odour/acne

Contents

Contents ...... 2 Description of Guideline ...... 2 Purpose of this document...... 2 Who should use this document...... 2 Patients to whom this document applies ...... 2 Definition of adrenarche ...... 3 Clinical features ...... 3 Biochemical findings ...... 3 Clinical significance ...... 3 Interpretation of clinical findings and investigation results: ...... 5 References ...... 6

Description of Guideline

Purpose of this document. To guide evaluation of a child presenting with features suggestive of adrenarche.

To guide the distinction between adrenarche, and other abnormalities of secondary sexual development.

Who should use this document. General practitioners, paediatricians and paediatric endocrinologists. Patients to whom this document applies Children presenting with pubic hair growth, axillary hair, body odour and acne before the expected age of puberty.

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Definition of adrenarche

Adrenarche is the gradual increase in adrenal secretion after approximately the age of 6 years in girls and 7 years in boys. It occurs independently from the gonadotrophin-dependent activation of the gonads in central puberty. Clinical features Adrenarche results in the development of pubic hair, axillary hair, body odour and acne. (It does not result in the enlargement of the , penis or testes). Biochemical findings At the time of adrenarche, there is maturation of the adrenal glands, with increased production of sulphate (DHEAS) relative to . The serum concentration of DHEAS can be used as a marker for the presence of adrenarche, with serum and levels being near the upper limit of the normal range. However, the diagnosis can be made on clinical features without further investigations (see next page) Clinical significance Adrenarche is a normal variant of pubertal development. It is important to distinguish this from precocious puberty and virilising conditions such as androgen secreting tumours and Congenital Adrenal hyperplasia. Adrenarche itself does not require treatment*. *There has been previous concern that adrenarche may be associated with the development of resistance, polycystic ovarian syndrome and metabolic syndrome, but this does not alter management or follow-up.

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PRIMARY or SECONDARY CARE SECONDARY CARE

Child Presents with the following Refer to Secondary Care. Clinical features: Investigations to exclude  Pubic/axillary hair Signs of central puberty? central precocious puberty:  Body odour  development   Acne  Testicular volume  4 ml YES   Baseline LH and FSH YES (On examination or reported by  Oestradiol/testosterone parents  Consider GnRH test Age Refer onwards if unable to assess) Girl < 8 years, Boy < 9 years? NO NO Signs of virilisation? Result interpretation:  Clitoromegaly No action required if no other  See page 3  Penile enlargement  Discuss results with concerning features. YES  On examination or reported by tertiary Endocrinologist Reassuree and Provide parents adrenarche information leaflet (Refer onwards if unable to assess)

 NO

Refer to Endocrinologist Age NO Initial investigations for girl <6 years, boy <7 years androgen secreting tumour and YES  Provide adrenarche congenital adrenal hyperplasia: information leaflet  Bone age  17 hydroxyprogesterone Review in 3-4 months:  Testosterone  Height velocity > 90th centile or YES   Androstenedione height increasing across centiles  DHEAS  Reassess for breast or testicular  Cortisol, ACTH development or virilisation  LH&FSH  Oestradiol  Consider urine steroid Reassure that consistent with NO profile if virilisation adrenarche and discharge 1

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Interpretation of clinical findings and investigation results

Breast/testicular Clitoral/penile Linear growth Bone Age Gonadotrophins development growth acceleration

Up to 2 years Early pubertal, advanced on Premature Absent, or slight DHEAS may be Absent Absent chronological age Prepubertal adrenarche initial acceleration moderately Correlated with elevated height age Stage 2+ breast May be normal or Early pubertal Precocious development Progressively Progressively elevated for age (If suppressed Absent or early puberty  4ml testicular accelerated accelerated Oestradiol may be consider oestrogen volume elevated secreting tumour)

Moderately or Congenital Moderately to markedly advanced Moderately to adrenal Absent Enlargement markedly Prepubertal for age and markedly elevated hyperplasia accelerated pubertal stage

Marked and Markedly and Markedly Prepubertal or Virilising tumours Absent progressive progressively Markedly elevated accelerated suppressed enlargement advanced

Marked and Markedly and Markedly Markedly elevated Prepubertal or Iatrogenic Absent progressive progressively accelerated testosterone suppressed enlargement advanced

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References

1. Williams RM, Ward CE, Hughes IA. Premature adrenarche. Arch Dis Child 2011; 97: 250-254. 2. Bourguignon JP, Rosenfield RL. Precocious . Practical Algorithms in Paediatric Endocrinology 2007 . 3. Ibanez L, Valls C, Marcos MV et al, Insulin sensitization for girls with precocious pubarche and with risk for polycystic syndrome: effects of prepubertal initation and postpubertal discontinuation of metformin treatment. J Clin Endocrinol Metab 2004; 89: 4331-7. 4. Ibanez L, Diaz R, Lopez-Bermejo A et al. Clinical spectrum of premature pubarche: links to metabolic syndrome and ovarian . Rev Endocr Metab Disord 2009; 10: 63-76. 5. Idkowiak J, Lavery GG, Dhir V et al. Premature adrenarche: novel lessons from early androgen excess. Eur J Endocrinol 2011;165:189-207. 6. Ghizzoni L, Milani S. The natural history of premature adrenarche. J Paediatr Endocriol Metabol. 2000;13 Suppl 5:1247-51.

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