Congenital Toxoplasmosis Presenting as Hypogonadotropic ... - MedIND

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Clinical Brief

Congenital Toxoplasmosis Presenting as Hypogonadotropic Hypogonadism P.S. Suresh Babu, K. Nagendra, R. Sarfaraz Navaz and H.M. Ravindranath Department of Pediatrics, J.J.M. Medical college, Davangere, Karnataka.

ABSTRACT A 17-yr-old boy presented with hypogonadotropic hypogonadism due to sequelae of intrauterine infection with Toxoplasma Gondii. Neuroendocrine manifestations of congenital toxoplasmosis are especially uncommon. It is our attempt to stress the importance of endocrine monitoring for early recognition of treatable sequelae. This may help to improve the quality of life in these patients. [Indian J Pediatr 2007; 74 (6) : 577-579] E-mail: [email protected]

Key words : Congenital toxoplasmosis; Chorioretinitis hypogonadotropic hypogonadism

Congenital toxoplasmosis has a spectrum of presentation varying from apparently normal to severe ocular and neurological involvement. Endocrine manifestations are extremely uncommon and have received little attention. Understandably, there are very few reports of this kind1 8 and none are from Asia. Here, we report a case of a 17 yr-old boy who presented with hypogonadotropic hypogonadism and displayed evidence of sequelae of congenital toxoplasmosis. CASE REPORT

rating of 1 as per tanner’s staging. His developmental age was 4 yr and IQ was 50. A clinical diagnosis of hypopituitarism was made. Laurence-Moon-Biedl (LMB) syndrome was a possibility and ultrasound abdomen was done to look for renal anomalies. It was normal. Retinal examination was done to detect retinitis pigmentosa which is known to have an incidence of 100% in LMB Syndrome. Retina did not show any evidence of retinal dystrophy or degeneration, instead, revealed evidence of healed choroiditis in macula in both eyes, which is typical of congenital toxoplasmosis (Fig. 2).

A 17-yr-old boy presented to us for non-attainment of secondary sexual characters, mental retardation, obesity (onset at 12 years of age) and decreased vision (onset at 10 yr of age)(Fig 1). He was the second born after a 32 week uneventful pregnancy to healthy parents of normal stature (father’s height – 175 cm; mother’s height – 160 cm). His elder sibling is apparently normal and healthy. His birth weight was 1.5 Kg and there was no history suggestive of birth asphyxia or other neonatal problems. On examination, his height was 122 cm (< 3rd centile as per NCHS data), weight was 40 Kg (> 95th centile as per NCHS data) and head circumference was 46.2 cm (< 5th centile). His short stature was proportionate. He had truncal obesity, a stretched penile length of < 2.5 cm, testicular volume of 2 ml each and a sexual maturity

Correspondence and Reprint requests : Dr. Suresh Babu P.S. M.D., D.C.H., Professor, Department of Pediatrics, JJM Medical College, Davangere-577004, Karnataka. Ph-08192-255131, Fax-08192-231388, [Received June 5, 2006; Accepted December 14, 2006]

Indian Journal of Pediatrics, Volume 74—June, 2007

Fig. 1. 17-yr-old male with Short Stature, obesity and hypogenitalism.

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P.S. Suresh Babu et al Aagard K 6 has reported congenital myxedema in congenital toxoplasmosis. No cases have been reported from Asia so far and only about 150 cases have been reported in world literature.

Fig. 2. Healed choroiditis Patch in Macula.

Laboratory evaluation revealed a significant increase in the toxoplasma IgG titer. Bone age was delayed (11-13 yr). Endocrinal evaluation suggested normal thyroid functions (TSH – 4-43 µIU/ml; free T3 – 3.28 pg/ml; free T4 – 1.04 ng/dl) and normal cortisol levels(9.4 µg/dl), but low levels of growth hormone (0.3 ng/ml), Luteinizing hormone (0.4mIU/ml), Follicle stimulating hormone(0.2mIU/ml) and testosterone (35 ng/dl). Plasma growth hormone was low throughout an insulin tolerance test (0 min – 0.3ng/ml; 30 min – 0.5ng/ml; 60 min – 0-46ng/ml; 120 min – 0-38ng/ml). However, this does not indicate presence of growth hormone deficiency since the secretion during puberty is stimulated by sex steroids which were low in this case. A GnRH stimulation test was withheld due to financial constraints. Urine osmolality and serum electrolytes were well within normal limits. These results suggest hypogonadotropic hypogonadism with no involvement of posterior pituitary. Computed tomography and magnetic resonance imaging reported a normal pituitary gland and bilateral calcification in the parieto-occipital regions. Mild cerebral volume loss with mild ventricular dilation indicative of a previous infective process was also noted. DISCUSSION Congenital toxoplasmosis is characterized by a meningoencephalitis with an intense perivascular inflammation involving particularly the basal ganglia and periventricular regions. It is likely that important hypothalamic regulatory centres are involved in this process resulting in hypothalamo-pituitary dysfunction. The clinical manifestations of toxoplasmosis result from direct tissue destruction by the parasite, but inflammatory cytokine mediated immunopathological changes may also contribute to disease progression. 1 Massa et al 2 reported three cases of congenital toxoplasmosis and hypothalamo-pituitary dysfunction. Setian et al3 and Bruhl HH4 reported precocious puberty and Oygur et al5 described central diabetes insipidus and 578

Most children with congenital toxoplasmosis are said to have been apparently normal at birth and the manifestations present weeks or mth later. Gershmann RN 7 in his series of 14 children with inborn neurotoxoplasmosis demonstrated that in prepubertal and pubertal periods, the prevalent symptoms are disorders of the hypothalamus. Massa et al2 has reported a case in his series of three cases where there has been delayed presentation at the age of 11 yr and 5 mth. Congenital toxoplasmosis is hence, recognized late when most sequelae have left irreversible imprints like microcephaly or macrocephaly, psychomotor retardation, visual deficits and seizures. Despite this disease being a well-known cause of intrauterine growth retardation, postnatal growth and development have hardly been evaluated in these children and systematic endocrine studies have not been performed. Needless to say, early recognition of endocrine sequelae and their prompt treatment with replacement therapy will go a long way in rehabilitation and improving the quality of living of these patients. In this patient, non-attainment of secondary sexual characters, short stature, obesity, microcephaly and hypogonadism made him a close differential diagnosis for LMB syndrome. However, ophthalmic examination was a strong clinching clue in favour of toxoplasmosis. The pituitary dysfunction in this child was only partial owing to normal cortisol response, posterior pituitary and thyroid functions. Abnormality noted was hypogonadotropic hypogonadism. Oktenli C reported that occasionally acute toxoplasmosis can also cause transient hypogonadotropic hypogonadism due to direct tissue injury or interleukin - 1β. At present, there are no parameters with which one can predict the outcome of asymptomatic infection. From the few cases reported so far, it is not possible to draw definite conclusions regarding the incidence of endocrinological disturbances in these children. Endocrinological sequelae, which are potentially treatable, should be anticipated and these children should be subjected to periodic evaluation. More studies would be required to derive a consensus on the timing, frequency and cost effectiveness of such testing. Also, congenital toxoplasmosis should be considered as one of the organic causes while evaluating children with pituitary disturbances. REFERENCES 1. Oktenli C, Doganci L, Ozgurtas T et al. Transient


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Congenital Toxoplasmosis Presenting as Hypogonadotropic Hypogonadism hypogonadotropic hypogonadism in males with acute toxoplasmosis: suppressive effect of interleukin - 1β on the secretion of GnRH. Human Reproduction 2004; 19(4) : 859-866. 2. Massa G, Vanderscheuren-lodeweyckx M, Van Vliet G, Craen M, De Zegher F, Eggermont E. Hypothalamo-pituitary dysfunction in congenital toxoplasmosis. Eur J Pediatr 1989; 148(8) : 742-744. 3. Setian N, Andrade RS, Kuperman H et al. Precocious puberty: an endocrine manifestation in congenital toxoplasmosis. J Pediatr Endocrinol Metab 2002 Nov-Dec; 15(9) : 1487-1490. 4. Bruhl HH, Bahn RC, Hayles AB. Sexual precocity associated with congenital toxoplasmosis. Mayo Clin Proc 1958; 33(26) : 682-686.


5. Oygur N, Yilmaz G, Ozkaynak C et al. Central diabetes insipitus in a patient with congenital toxoplasmosis. Am J Perinatol 1998 Mar; 15(3) : 191-192. 6. Aagaard K, Melchior J. The simultaneous occurrence of congenital toxoplasmosis and congenital myxedema. Acta Paediatr 1959; 48(2) : 164-168. 7. Gershman RN. Toxoplamosis hypothalamic syndromes in children. Zh Nevropatol Psikhiatr Im S S Korsakova 1979; 79(2) : 172-175. 8. Coppola A, Spera C, Varcaccio GG, Gargiulo A et al. Partial anterior hypopituitarism caused by toxoplasmosis congenital. Description of a clinical case. Minerva Med 1987; 78(6) : 403-410.

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