1Department that Pediatric Gastroenterology, university of Miami-Jackson wellness System, 1601 NW 12th Ave, Miami, FL 33137, USA

2Department the Pediatrics, division of Pediatric Endocrinology, Richmond University clinical Center, 355 Bard Ave, Staten Island, new York, NY 10310, USA


A newborn male child was admitted to the neonatal intensive treatment unit because of suspected sepsis. He was clinically stable with common electrolyte levels on admission. However, he was detailed to have micropenis and also bilateral nonpalpable testes. Ultrasound imaging evidenced the presence of both gonads in the inguinal canal, through no Müllerian structures visualized. Activities examination revealed one undetectable random plasma cortisol level; subsequent ACTH stimulation testing evidenced adrenal insufficiency. Further testing revealed added pituitary hormone deficiencies, and the child was started on multiple hormone replacement therapies. Magnetic resonance imaging identified absent septum pellucidum, pointing of the frontal horns, and also optic nerve hypoplasia. A diagnosis that septo-optic dysplasia was made based upon this mix of findings. This case highlights the prestige of thorough physical examination in newborn infants, which might reveal the just sign of basic pathology in the absence of other concerning findings.

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1. Introduction

Formerly known as de Morsier’s syndrome, septo-optic dysplasia (SOD) wake up in 1 out of every 10,000 live births. That is a clinical diagnosis including at the very least two of the following: midline brain defects (e.g., septum pellucidum and/or body callosum agenesis), optic nerve hypoplasia, and hypopituitarism. The phenotype is change as many patients carry out not exhibition all 3 findings <1>.

Hypopituitarism is the most usual clinical detect in SOD, observed in 62–80% of patient <2>. Suggestive features encompass hypoglycemia, cleft lip and/or palate, micropenis, undescended testes, and an extensive jaundice <3>.

We report a situation of SOD diagnosed in a newborn infant who presented with micropenis and also bilateral undescended testes. The infant was otherwise clinically well with persistently normal electrolytes, including normal blood glucose levels. However, his exam findings prompted comprehensive diagnostic evaluation, and also he was ultimately diagnosed v SOD based on laboratory and magnetic resonance imaging (MRI) results. This instance report underscores the prestige of a complete physical check in child infants, including a genital exam as atypical genitalia may be the just presenting authorize of hypopituitarism and SOD.

2. Situation Presentation

A newborn male infant was born in ~ our college at 41 weeks of gestation via typical spontaneous vaginal shipment to a 20-year-old G1P0 mom with an adverse prenatal serologies and normal prenatal ultrasounds. There was no known family history of endocrine problems or midline defects or background of consanguinity in between the parents. Birth weight was 3.71 kg. The patient was vigorous after birth, with Apgar scores that 9 at 1 minute and also 9 in ~ 5 minutes. However, due to maternal fever, the child was admitted come the neonatal intensive care unit because that suspected sepsis.

On physics exam, the infant was provided to have stretched penile length of 1.5 cm. Neither testis to be palpable in the scrotum or inguinal canal. The remainder that the exam was unremarkable, with no slot lip, cleft palate, or other dysmorphic features.

Initial activities evaluation showed normal electrolytes (sodium 137 mmol/L, potassium 3.5 mmol/L, and also glucose 4.5 mmol/L). Scrotal ultrasound shown that both testes were current in the inguinal canal. No uterus or ovaries to be seen. Pediatric endocrinology was consulted, and multiple activities tests were ordered to evaluate pituitary, adrenal, and also gonadal functions. Pertinent outcomes are presented in Table 1.

Patient’s period in job at the time of blood drawValueUnitsReference varieties for age
Plasma glucose24.5mmol/L3.9–5.6
Random cortisol4µIU/mL1.3–16
Free T41311.6pmol/L10.8–63.9

The patient’s cortisol level resulted very first as undetectably low, which triggered an ACTH stimulation test. A high-dose stimulation test to be performed together it to be unclear at that time whether cortisol deficiency was primary or secondary. Cortisol levels attracted at 30 and also 60 minutes were both 24.8 nmol/L, continual with suboptimal an answer and adrenal insufficiency. Within this context, the low insulin-like expansion factor 1 and insulin-like development factor-binding protein levels to be suggestive of development hormone deficiency. Expansion hormone stimulation testing was no performed as result of patient’s young age. Thyroid role tests revealed central hypothyroidism, with inappropriately common thyroid-stimulating hormone (TSH) level in the setup of borderline low complimentary thyroxine (T4) level. There to be no evidence of diabetes insipidus. The patient’s salt levels ranged 137–143 mmol/L, and also mean urine output was 1.3 mL/kg/hour.

Given these findings, the patient was started on growth hormone, levothyroxine, and hydrocortisone therapy. Succeeding MRI revealed a little pituitary gland, missing septum pellucidum, and also pointing the the frontal horns, consistent with a diagnosis the septo-optic dysplasia (Figure 1). Laboratory evaluation at three months the age, during minipuberty of infancy, again confirmed low total testosterone level (0.73 nmol/L).


Starting at 6 months the age, the patient underwent a quick course the intramuscular testosterone treatment for micropenis, receiving 25 mg testosterone once monthly because that a full of three doses. Stretched penile size after therapy completion was 3 cm, in ~ 2.5 typical deviations for age. Ours patient likewise underwent orchiopexy in ~ 8 and 11 months of age, receiving perioperative hydrocortisone anxiety dosing because that both surgeries.

Our patient has been evaluated by a pediatric ophthalmologist, who shown the existence of optic nerve hypoplasia. Together of 18 month of age, that is tracking well with complete extraocular muscle movements and also has not, hence far, compelled eyeglasses. He has actually been receiving occupational and physical therapy due to the fact that 9 months of age. The patient has actually been referred because that genetic analysis but has not yet undergone evaluation.

3. Discussion

The presence of bilateral undescended testes in a gene 46, XY masculine infant suggests either a defect in androgen activity (such as partial 5-α reductase deficiency or partial androgen insensitivity syndrome) or a defect in androgen production, likewise known as hypogonadism <4>.

Hypogonadism, in turn, can occur at either the main or peripheral level. Reasons of congenital central, or hypogonadotropic, hypogonadism encompass pituitary defects such together Kallmann syndrome, septo-optic dysplasia, and also adrenal hypoplasia congenita. The visibility of midline defects such together cleft lip, cleft palate, solitary main incisor, and omphalocele makes a pituitary defect much more likely <5>. Conversely, differential diagnoses for congenital hypergonadotropic hypogonadism incorporate Klinefelter syndrome, partial gonadal dysgenesis, and also enzymatic defects in adrenal testosterone biosynthesis <6>.

Our patient presented v both undescended testes and micropenis, i beg your pardon is also associated with hypogonadism. Micropenis is identified as penile size less than 2.5 conventional deviations below the mean. A extended penile size measurement is critical in bespeak to distinguish true micropenis from situations where the penile base is hidden <4>.

Infants through suspected hypogonadotropic hypogonadism have to undergo complete pituitary hormone evaluation. Hypoglycemia, i m sorry is linked with both growth hormone and also cortisol deficiencies, can be secondary suggestive finding. Interestingly, our patient to be normoglycemic throughout his hospitalization, in spite of having multiple pituitary hormone deficiencies. The visibility of low development hormone and/or cortisol levels throughout hypoglycemia can assist in diagnosing deficiencies of these hormones <7, 8>. ACTH stimulation testing with cosyntropin is frequently used to check cortisol deficiency <3>. Thyroid function tests and also serum/urine osmolality should additionally be monitored to evaluate for central hypothyroidism and diabetes insipidus, dong <9, 10>. Importantly, pituitary hormone deficiencies can construct over time, for this reason close endocrine follow-up is important <1>.

Hypogonadism itself can be confirmed throughout minipuberty the infancy, which wake up in boys up to age 6 months and also in girl up to period 3 years <11>. Along with laboratory testing, MRI of the brain should be acquired to advice the morphology the the pituitary gland (including the visibility of the posterior pituitary shining spot), body callosum, septum pellucidum, optic nerves, and also optic chiasm <2>.

Patients with hypopituitarism should receive replacement of any deficient hormones. Households of patients with adrenal insufficiency should be counseled ~ above steroid tension dosing during times the illness and emergency <8>. Infants with micropenis deserve to be treated through a quick course the testosterone in order to increase penile length. A dosing regimen the 25 mg IM, given every 3 or 4 main for 3 doses, has been efficiently implemented <2, 5>.

Of note, testosterone therapy has actually been associated with reduced Sertoli cell role and spermatogenesis <12>. Recombinant FSH therapy throughout minipuberty, in mix with testosterone therapy, has actually been displayed to boost Sertoli cell function in the brief term, back longitudinal data space not available <13>. Object dihydrotestosterone (DHT) has also been presented to boost penile length in patients through micropenis as result of various hereditary conditions, v minimal adverse effects. Again, data regarding precise dosing and also long-term impacts are not easily accessible <4, 14>.

Patients through cryptorchidism who testes have actually not lower by 6 months of period should undergo orchiopexy within the next year <15>.

Patients v SOD should follow through a multidisciplinary team, with administration aimed at treating pituitary hormone deficiencies, providing neurodevelopmental support, and also monitoring because that visual disability <1>.

4. Conclusion

A thorough physical examination is crucial in newborn babies as it have the right to reveal indicators of a serious underlying condition. The visibility of micropenis and bilateral undescended testes in a 46, XY infant should prompt assessment because that hypogonadism. In cases of doubt hypogonadotropic hypogonadism, a complete pituitary hormone workup should be undertaken follow me with mind imaging to additional clarify the diagnosis. Septo-optic dysplasia is a rare however important cause of hypopituitarism, which necessitates monitoring by a multidisciplinary team that specialists. Patients with SOD need to be carefully monitored for the potential development of additional pituitary hormone deficiencies over time.

Conflicts of Interest

Dr. Palorath and also Kharode declare no conflicts of interest.

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The writer would like to give thanks to Dr. Amita De Souza for she contributions come this manuscript.

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