Delayed puberty / Hypogonadism

 

• Puberty is considered to be delayed if the onset of the physical features of sexual maturation has not occurred by a chronological age that is 2.5 standard deviations (SD) above the national average. 
• In the UK, this is by the age of 14 in boys and 13 in girls. 

 

History:

• History of present illness:

• chronic illness : renal, cardiac, hepatic  → eg. hemochromatosis

• lethargy, weight gain, cold intolerance, somnolence → hypothyroidism

• fever, convulsion, disorientation  → TB, TB meningitis, meningioma, ICSOL, lymphoma 

• headache, visual disturbance, diplopia —————————-→ pituitary macroadenoma

• galactorrhea, amenorrhea ————————————————–→ hyperprolactinemia

• weight gain, bruising, striae, muscle weakness, new onset DM, HTN → Cushing syndrome 

 

• Previous or current medical disorders: 
  • medical record review
• Past history: 
  • genital disease: trauma, TB, surgery
  • painful swelling → mumps

 

• • Treatment history: 
    • chemotherapy, radiotherapy

• Family history: 

• parents/siblings: age of menarche 

• ethnicity, parenteral/siblings height

• Personal history/Occupational history: 

• excessive physical exercise/elite athletes

• feeling of libido 

• unprotected sexual exposure: HBV, HCV, HIV, syphilis

 

• Menstrual history:
  • cycle regularity, menstrual period, blood flow

 

• Obstetrical history/Gynaecological history:
  • recent pregnancy, mood of deliver, bleeding, lactation failure → sheehan syndrome  

• Psychiatric history: 

• avoidance of food, concern regarding weight gain ——————→ anorexia nervosa

• psychological distress, H/O childhood abuse 

Examination:

• Nutritional status 
• BMI : 
  • low → chronic systemic illness, malnutrition, anorexia nervosa, 
  • high → primary hypothyroidism, cushing syndrome 

 

• Tall stature with disproportionately long arms & legs relative to trunk, anosmia

——————————–→ kallmann syndrome 

• Growth charts: 
  • plotting with current height, weight and age of the patient along with parental height
  • Healthy growth: usually follows a centile.
  • constitutional delay: 

1. children are healthy, maintain a normal growth velocity 
2. small in size, > 2 SD below the mean height for their age throughout childhood

 

• acquired disease: poor linear growth, with ‘crossing of the height centiles’

 

• Breast examination: 
  • gynaecomastia: hypogonadotropic hypogonadism. 
  • any discharge
• Genital examination: 
  • absence of testes in the scrotum → cryptorchidism
  • enlarged testes → malignancy 
  • hydrocele → TB, malignancy

• Rapid, low volume pulse, hypotension with postural drop 

• • adrenocortical insufficiency → autoimmune, TB, hemochromatosis, HIV, infiltration

 

• Lymphadenopathy,  hepatomegaly, splenomegaly: —————————–TB, lymphoma, leukemia 
• Organomegaly, DM, skin pigmentation —————————————-→ hemochromatosis 
• F/O Klinefelter syndrome / Turner syndrome

 

Investigations:

 

Investigations	Finding
Testosterone (boy) Estradiol (girl)	low
LH, FSH	high → primary / gonadal :  chemo/radio, mumps, autoimmune, TB, traumatic, malignancy, hemochromatosis  low → secondary / constitutional
X-ray wrist and hand	bone age < chronological age → constitutional delay
karyotyping  (chromosomal analysis)	adolescents with hypergonadotrophic hypogonadism, to exclude Turner and Klinefelter syndromes
To detect systemic illness
CBC, PBF, ESR, CRP	anemia →  normocytic → ACD microcytic hypochromic → thalassemia → secondary hemochromatosis  Megaloblastic anemia → pernicious anemia, Coeliac disease (APS-2) high ESR, high CRP → infection, inflammation
S creatinine, electrolytes, urea	renal impairment → CKD
SGPT, PT, Albumin	chronic liver disease
TSH, T4 S cortisol	T4: low TSH  high → primary (> 20) → autoimmune disease undetectable/ detectable (< 20) → secondary cortisol low → autoimmune disease, TB, hemochromatosis
To see structural abnormality (suspected secondary) CT or MRI brain	suspected secondary
To see pituitary function ACTH, TSH, T4,

 

Management 

• Medical induction of puberty: 

• low doses of oral estrogen in girls (e.g. ethinylestradiol) or testosterone in boys (testosterone gel or depot testosterone esters). 

• higher doses carry risk of early fusion of epiphyses. 

• Needs specialist care. 

• In children with constitutional delay:  

• above ‘priming’ therapy is discontinued when endogenous puberty is established, usually in < 1 year. 

• In children with hypogonadism:
  • treatment of underlying cause and reversal, if possible. 
  • if hypogonadism is permanent, sex hormone doses are gradually increased during puberty and full adult replacement doses given when development is complete.