CASE 18- A Case of extreme short stature with Delayed puberty

Original case by Deep Dutta et al


A 16-year-old girl presented with short stature noticed since 10 years of age along with lack of puberty. She had normal childhood, without any history of failure to thrive, head injury or polyuria. Maternal age of menarche was 14 years.

Q What are the differential diagnosis of short stature with primary amenorrhea at this age ?

  1. Constitutional delay
  2. Turner’s syndrome
  3. Other causes of Gonadal dysgenesis
  4. Hypogonadotrophic hypogonadism
  5. Panhypopituitarism

Q What are points against CDGP ?

Mother had menses at 14 years of age. CDGP generally have family history of delayed puberty.


Examination revealed significant short stature (Height 127.2cm; standard deviation. -6.06), multiple  facial nevi (Fig. 1a), cubitus valgus and goiter. Sexual maturity rating was pre-pubertal. Bone age (Greulich Pyle) was 10 years.

Q What is the definition of short stature based on Standard deviation ?

Short stature is defined as height of child 2 Standard deviation below the mean for the chronological age and sex of the child.

Q This SD corresponds to what percentile ?

This corresponds to 2.3 percentile.

Q Based on the clinical examination findings what is your differential diagnosis and why ?

The differential diagnosis goes strongly in favour of Turner’s syndrome after history and examination. The points in favour are:

  1. Patient has extreme short stature with absence of secondary sexual characteristics.
  2. Cubitus vulgus
  3. Presence of Goiter
  4. Delayed bone age

Q Are nevi common in patients with Turner’s syndrome ?

Yes. Nevi are more common in patients with Turner’s than in general population. However, melanoma risk is not increased.

Q Which rare skin neoplasm is common in Turner’s syndrome ?

Pilomatricoma. This is a rare skin neoplasm arising from cells of the hair follicles. They present as asymptomatic papules.


Ultrasonography revealed infantile uterus with lack of visualization of ovaries. Karyotype was 45,X. Height plotted on Turner syndrome specific growth chart (TSGC) was <5thpercentile. Hormonal evaluation revealed secondary hypothyroidism and hypogonadism (low basal and post GnRH analogue stimulated LH).  Serum electrolytes were normal.

Anti thyroid peroxidase antibody titer was elevated (224 U/mL; normal <35 U/mL). Serum IgA antitissue transglutaminase antibody levels were normal (0.2 AU/mL; normal <8 AU/mL).

Hormonal profile (Table)

Q The patient has hypothyroidism. What is unusual about it ?

Primary hypothyroidism , mainly autoimmune is not uncommon in Turner’s syndrome. However, as per the case report the patient has secondary hypothyroidism which is unusual.  Also the LH and FSH are generally elevated in patients with Turner’s syndrome. In this case they are low.

Q Why are is anti TTg done in this case ?

To rule out Celiac disease. Again, celiac is not uncommon in patient with Turner’s syndrome.

Q What is the interpretation of the clonidine stimulation and insulin tolerance test in this case ?

They are suggestive of GH deficiency.

Q What is the importance of Turner specific growth chart ?

The patient is having short stature even as per the Turner specific growth chart. This means the patient potentially has other causes of short stature which need to be ruled out. If a patient has <  3rd percentile on Turner specific growth chart than additional evaluation for short stature etiology is mandated.

Q Is growth hormone stimulation test routinely necessary in patients with Turner’s syndrome ?

No. It is not routinely advised.

Levothyroxine was started at 50 μg/day. Evaluation of GH status 4 weeks later revealed GH deficiency (Web Table I). Magnetic resonance imaging (MRI) of brain revealed empty sella with ectopic neurohypophysis near tuber cinerium.

Q What is the MRI features of Congenital hypopituitarism ?

  1. Ectopic posterior pituitary
  2. Small anterior pituitary (or empty sella)
  3. Deviated anterior pituitary stalk

Q Why was the GH stimulation test done after correcting the hypothyroidism ?

The response of GH to stimulation may be subnormal if patient is having hypothyroidism. Hence thyroid should be corrected before GH stimulation testing.

Q What is the normal response of GH on stimulation ?

Generally GH >10 ug/l is considered to be normal on stimulation.


GH was started at 3 U/night subcutaneously, increased to 4.5U/night after three months.

Q What is the dose of GH in patients with Turner’s syndrome ?

The dose is generally 50 ug/kg/day ie 0.375 mg/kg/week Q How will you convert dose of GH from  milligram to International units ?

3 IU = 1 mg of Growth hormone. The dose in Turner would be 0.16 units/kg/day

Ethinyl-estradiol 2.5 μg/day was also started, along with calcium and vitamin-D. Reassessment was done 6 monthly. Ethinyl-estradiol was increased by 2.5 μg every 6 months.

  1. How is Pubertal induction and Estrogen therapy administered in patients with Turner’s syndrome ?
  2. Age of 12
    1. Start estrogen therapy
    2. Ethinyl estradiol preferred – PROGYNOVA (or T. EVALON) 0.25 mg (1/4th tablet) once a day
    3. If Progynova not available then Conjugated estrogen – PREMARIN – 0.625 mg once a day may be given as alternative
    4. Gradually increase the dose every 3-6 months till age of 14 years
      1. T Progynova- 0.25 mg increase every 3 month 0.25 – 0.5 mg -1 mg – 1.25 mg – 1.5 mg – 1.75 mg – 2 mg. Scoring of tablet may be difficult so you can increase by ½ tablet (0.5 mg) every 6 months
      2. T. Premarin – 0.625 mg increase every 6 months- 0.625 mg – 1.25 mg – 1.875 mg- 2.5 mg
    5. 14 years of age
      1. Patient now receives adult dose of Estrogen. Estrogen generally given from days 1-25.
      2. Progesterone may be added cyclically (may be added earlier if breakthrough bleeding occurs)
        1. C. ALGEST / ENDOGEST – 200 mg on day 20-30 of cycle
        2. T. MEPRATE (Medroxyprogesterone) –2.5- 5 mg on days 20-30

She gained 5 cm height in first 6 months, 3 cm in next 6 months, and 3 cm in next 1 year when GH was stopped. Two years after diagnosis, her height was 138.2 cm (Fig. 1c), had B3 breast development, and was on 10 μg of ethinyl-estradiol.

Following breakthrough bleeding, patient has been receiving monthly medroxypro-gesterone along with ethinyl-estradiol for the last three months, ensuring regular menses.


Q What is the typical GH profile in patients with Turner’s syndrome ?

They have

  1. Increased IGFBP3
  2. Reduced IGF1
  3. Normal GH stimulation

Q What are the indications for stopping GH Therapy in Turner’s syndrome ?

Therapy with GH is  continued till growth potential remains. Stopped when:

  1. Bone age >14 years
  2. Growth velocity <2 cm / year

Q Should oxandrolone have been added to this case ?

Yes. Turner’s patients with age >9 years have additional benefit with Oxandrolone.

Q Which additional evaluation should have been done for this patient ?

Cardiovascular evaluation at baseline must be done in all Turner’s patient. This includes:

Baseline evaluation

  1. All four limb blood pressure measurement
  2. ECG at baseline
  3. Echocardiography at baseline
  4. Older girls and adults also need to get done cardiac MRI
  5. If anything abnormal- refer to cardiologist
  6. If everything normal – follow up
  1. Which other investigations must be asked for in Child with Turner’s syndrome ?
  1. Ultrasound KUB – to rule out urinary tract abnormality
  2. ENT reference for assessment of hearing function
  3. Ophthalmology reference for visual assessment
  4. Child growth and psychological assessment must be done

They have problems in visuospatial, social cognition and non-verbal problem solving

Learning Points from this case

All children with Turner’s syndrome should have their height plot on Turner specific growth chart. If the chart shows height <  3rd percentile than additional evaluation for other causes of short stature is required


One thought on “CASE 18- A Case of extreme short stature with Delayed puberty

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s