Keywords: pituitary stalk blockade syndrome, gonadal dysplasia (hypogonadism); embryological; pathogenesy History: male child, 10 years and 3 months old, presented to the hospital with 10 years of slow growth. Home delivery, full term and normal, pregnancy due to failed emergency contraceptive pill, birth weight 2.5+ kg, birth length unknown, short penis at birth, parents did not pay attention to it. Father 162 cm, mother 162 cm. No visual or olfactory abnormalities. His academic performance was low (parents reported that he scored 70+ in language and mathematics in last year’s final exam), and his height increased by about 1 cm in the last six months (parents’ oral report). He was physically fit and had no history of convulsions, coma, encephalitis or cranio-cerebral trauma. Appetite was poor, stool was OK, no polyhydramnios, polyuria, sleep was OK, little movement, cold fear. Physical examination: slightly depressed, height 107.0 cm, weight 17.2 kg, sitting height 60 cm, finger spacing 107 cm, blood pressure: 80/58 mmHg, no special facial features, slightly pale; heart rate 95 beats/min, clear respiratory sounds in both lungs, no dry and wet stalls Huanwei (2) (10) Cui duck E compo dumpling ash staggering leaning (19) pie often bang and ladle. ( !1ml), soft texture; penis small, about 15-17mm long, circumference 6-7mm. no special extremities, no coffee milk spots in the whole body, skin mucous membrane coloration is not deep.
Auxiliary examinations: TSH: 3.977uIU/ml, FT4: 0.57ng/dL. IGF-1 less than 25ng/ML. liver function, kidney function normal, fasting blood sugar: 4.77mmol/L, ion six normal (blood sodium: 138.5 mmol/L, blood potassium: 3.76 mmol/L, blood chloride: 105.6 mmol/L, serum phosphorus. 1.33 mmol/L, serum magnesium: 0.80 mmol/L, serum calcium: 2.30 mmol/L). Routine blood cues: Hb:106g/L, MCV, MCH, MCHC normal, WBC: 6.61*10E9/L, LYMPH %: 47.8%. Testosterone: <10ng/dL, estradiol: 51.27pg/ml, progesterone: <0.15ng/ml, prolactin: 19.93ng/ml. Gonadotropin-releasing hormone stimulation test (stimulated with Dabigat): LH (chemiluminescence) <0.07mIU/ml at 0, 30, 60, 90, 120 minutes, FSH (chemiluminescence) at 0 Growth hormone stimulation test (stimulated by arginine hydrochloride and levodopa simultaneously): GH peak: 0.15ng/ml. 8-9am: ACTH: 3.13pmol/L (reference range: 0-10.12pmol/L), cortisol: 134nmol/L (reference range: 138-690nmol/L). Ultrasound: left testicle: 10*10*5mm, right testicle: 9*7*5mm. no significant uterus and ovaries detected in the pelvis. CHN bone age was equivalent to 4.4 years. MRI diagnosis: Consider pituitary stalk block syndrome, please combine with clinical laboratory examination. Diagnosis: pituitary stalk block syndrome (PSIS). (Secondary hypoadrenocorticism, central hypothyroidism, complete lack of growth hormone, hypogonadotropic gonadal dysgenesis). Treatment and follow-up: Cortisone acetate was given orally twice a day, 10 mg in the morning and 5 mg in the afternoon. 12.5 mcg of levothyroxine sodium was given orally once a day after one week. Growth hormone 2IU was administered subcutaneously. HCG 1000 IU was administered intramuscularly twice a week. The child’s parents were informed of the possible risks of adrenal crisis. 3 weeks later: mental status improved, testosterone: 15 ng/dL, TSH: 0.888 Uiu/ml, FT4: 0.78 ng/dL. cortisol: 952.00 nmol/L (reference value: 138-690 nmol/L) Ultrasound of testes: left testis: 11*9*7 mm, right testis: 11*8 mm. The dose of medication was further adjusted and after 2 months of treatment, the height increased from 107.0 cm at the beginning to 111.0 cm and the weight increased from 17.2 g to 18.0 kg. Discussion: Pituitary stalk interruption syndrome (PSIS) is a clinical series of symptoms caused by the absence or significant thinning of the pituitary stalk, combined with ectopic posterior pituitary gland, and the failure of hormones secreted by the hypothalamus to be delivered to the pituitary gland through the pituitary stalk, resulting in anterior pituitary hypoplasia. The pathogenesis of the disease is unclear and most believe that it is related to perinatal abnormalities (breech position, foot first, cesarean section, preterm birth and postnatal asphyxia) or craniocerebral trauma. Sheelan and Whiteheda found that the pituitary stalk was easily broken at autopsy, and both domestic and foreign scholars have suggested that delivery abnormalities are a major factor in PSIS [4,5]. In this case, there was a history of emergency contraceptive use before pregnancy, and the parents reported that the child was born with a short penis (the child was 10 years old and his penis length was less than the lower limit of 2 cm of normal full-term neonatal penis length, and perinatal abnormalities would only result in no testicular penile growth after birth, and the penis length should be greater than this value). The pituitary gland may have developed abnormally during pregnancy, resulting in poor gonadal development, and not only during the perinatal period. GnRH can be found in the olfactory substrate as early as 5.5 weeks of embryonic life and in the hypothalamus after the 9th week. The adenohypophysis secretes LH and FSH in response to GnRH, the latter further promoting testicular and penile development during fetal life. The pituitary gland is divided into the adenohypophysis, which is derived from the Rathke pouch, and the neurohypophysis, which is derived from the neurohypophysis bud. In the third week of embryonic development, the Rathke pouch and the pituitary bud form and gradually grow close to each other, the pituitary gland gradually thins at the beginning to form a funnel stalk, and the anterior pituitary gland grows nodularly upward and wraps around the funnel stalk. The fetal gonads can continue to develop in the absence of GnRH, FSH, and LH in the presence of maternal HCG. 311 cases of pituitary stalk block syndrome MR revealed 62 cases of pituitary thinning, 215 cases of ectopic posterior pituitary lobes, 2 cases of agenesis of the corpus callosum, and 1 case of pituitary tumor [7]. Does this situation suggest that abnormal pituitary development during the embryonic period may be the main cause of the disease? In conclusion, the exact pathogenesis of the disease has to be studied more thoroughly. In children with slow growth, a careful perinatal history should be taken, a systematic physical examination should be performed, with special emphasis on the development of the gonads, and a comprehensive evaluation of anterior pituitary hormone levels and routine pituitary MRI, the latter being the most reliable method to confirm the diagnosis of PSIS; those diagnosed with PSIS should be given appropriate replacement therapy according to their type of hormone deficiency.