Clinical Neurology and Neurosurgery 104 (2002) 367– 370
Familial colloid cyst of the third ventricle: neuroendocrinological follow-up and review of the literature Herna´n Valde´s Socin a,b,*, Jacques Born b, Caroline Wallemacq b, Daniela Betea a, Jean Jacques Legros a,b, Albert Beckers a b
a Department of Endocrinology, Centre Hospitalier Uni6ersitaire Sart Tilman, B35 Lie`ge, Belgium Department of Endocrinology and Neurosurgery, Centre Hospitalier Re´gional La Citadelle, Lie`ge, Belgium
Received 28 June 2001; received in revised form 15 December 2001; accepted 10 January 2002
Abstract Colloid cysts of the third ventricle are rare, benign cysts of endodermal origin. Between 1989 and 1999, eight patients with this lesion (five females, three males), with a mean age of 40.5 years (range 20 – 54), were identified out of 1354 operated for tumours of the central nervous system. Among the eight, two were familial. They were half sisters 38 and 28 years-old, who were diagnosed to have colloid cysts of the third ventricle on CT scanning. Transcortical excision yielded 10 and 15 mm sized colloid cysts, respectively. Moreover, both sisters developed a multinodular goiter associated with these congenital tumours. The second sibling developed hyperprolactinemia associated with macroprolactinemia. Pregnancy was only possible after bromocriptine treatment. These cases provide further evidences that colloid cysts probably have an autosomic recessive pattern of inheritance with variable penetrance. © 2002 Published by Elsevier Science B.V. Keywords: Familial; Third ventricle; Colloid cyst; Macroprolactinemia; Goitre
1. Introduction Colloid cysts of the third ventricle represent 0.5 –1% of intracranial tumours. These benign and congenital tumours are considered to be an ectopic endodermal migration in the velum interpositum during development of the central nervous system. They may constitute a potential life threat because of acute obstructive hydrocephalous [1– 3]. The clinician, the radiologist and the neurosurgeon should also be aware of some rare clinical conditions that have been described together, such as craniopharyngioma , astrocytoma , capillary hemangioma of the choroid plexus , xanthogranuloma [7,8] and agenesis of the corpus callosum [9,10]. Familial cases have been previously considered as an extremely rare condition. The probability of a colloid cyst occurring by chance in a kinship has been calculated as one in 1010 . * Corresponding author. Tel.: +324-366-7083/84; fax: + 324-3667261. E-mail address: [email protected]
Some authors suggest a possible autosomal recessive inheritance but a genetic abnormality is as yet unknown. Since 1986, when the first familial case was described in identical twins, only six reports of such cases have been published [1,3,11 –14]. We describe two new cases and review the available literature. We also report neuroendocrinological follow-up of these cases. One of them is associated with macroprolactinemia and had been followed up during pregnancy.
2. Results Between 1989 and 1999, eight patients with colloid cyst of the third ventricle (five women, three men), with a mean age of 40.5 years (range 20–54) were identified among 1354 intracranial tumours operated upon in our centre. Among these eight cases historytaking revealed two familial cases, which had a neuroendocrinological follow-up.
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H.V. Socin et al. / Clinical Neurology and Neurosurgery 104 (2002) 367–370
Fig. 1. The pathological examination of the removed material (Patient 1), showed an epithelial lined cyst. The epithelium was made up of one or more lines of cylindric cells. The content of the cyst was composed by mucus and polysaccharides staining with PAS. Tumoral markers GFA, S100, NSE and VIM were negative.
3. Case reports
3.1. Patient 1 This 38-year-old woman presented holocranial headaches since about 1 year in 1985. The cerebral CT scan revealed a mass lesion of the third ventricle associated with hydrocephalus involving the lateral ventricles. Through a right transcortical approach the tumour appeared as a green mass of 10 mm diameter, adherent to the adjacent choroid and vascular structures. The pathological examination identified a colloid cyst (Fig. 1). Two months later, endocrinological follow-up revealed an euthyroid and non compressive goiter. Pituitary hormones were normal.
the diagnosis of colloid cyst (Fig. 2). Six months after the operation, clinical examination revealed a small and euthyroid goitre. PRL was 318 mU/ml. There were no markers of thyroid autoimmunity. TRH test showed a normal response of TSH and a sustained elevation of PRL at 2452 mU/l. The 131I thyroid scintigraphy revealed an homogeneous goiter. Pituitary magnetic resonance imaging (MRI) showed an increase of the pituitary volume without a defined intrasellar lesion. Two years later, the patient developed hypothyroidism and bilateral galactorrhea with a moderate hyperprolactinemia responsive to TRH stimulation. Due to the patient’s desire for fertility, treatment with 100 mg of levothyroxine and 5 mg/day of bromoergocriptine (BEC) was started. Three years after the diagnosis of colloid cyst had been made, the patient became preg-
3.2. Case 2 In 1989, the half-sister complained of severe headaches. This 28 year-old woman presented bilateral galactorrhea with regular menses. Neuroendocrinological assessment revealed a prolactin (PRL) of 650 mU/ ml (normal range: 150– 600) that increased to a maximum level of 1832 after TRH stimulation, in the absence of hypothyroidism or thyroid autoimmunity. Cerebral CT scan revealed a mass lesion of 10 mm in the third ventricle associated with ventricular dilatation (Fig. 2). Cerebral nuclear magnetic resonance showed a colloid cyst located in an unusually high position of the anterior part of the third ventricle. Surprisingly, no pituitary lesion was identified. The colloid cyst was removed by a right frontal transcortical excision. Pathological studies confirmed
Fig. 2. CT scan (Patient 2), showing hyperdense midline lesion at the level of the foramen of Monro. There is a 15 mm colloid cyst and ventricular dilatation.
H.V. Socin et al. / Clinical Neurology and Neurosurgery 104 (2002) 367–370 Table 1 Levels of PRL, Big-big PRL and Big PRL before, during and after pregnancy in patient 2
Without treatment Under BEC 5 mg/day First trimester Second trimester Delivery
2433 3593 1700
29 22 30
25 28 16
Nd: not detectable, BEC was stopped during pregnancy.
nant. The results of prolactin chromatography (Superdex 200 HR 10/30, FPLC System®, Amersham Pharmacia Biotech, the limit of detection is 200 mU/l of prolactin) and follow-up are shown in Table 1. Pituitary MRI during pregnancy demonstrated a hyperplastic gland without evidence of adenoma. PRL levels are currently normalised under cabergoline 0.5 mg per week. The mother and two brothers were screened by CT scan and found to be unaffected. Both fathers of these kindred had previously died of a heart attack and were not screened.
4. Discussion In our limited surgical series, familial presentation represents 2/8 instances, and seems therefore not negligible. Six reports of familial cases of colloid cyst of the third ventricle have been published, but no data on the incidence of familial cases are available (Table 2). In the family reported here, consanguinity was ruled out. We describe two affected and symptomatic siblings, and screened radiologically three non-affected
siblings. Genetic analysis was not performed in our patients. Nader-Sepahi et al.  stated that no chromosomal abnormalities were found in three affected siblings. Our report and others [13,14], argue for a probable autosomal recessive inheritance pattern. Some clinical features in this family deserve further commentary, such as the finding of a non-toxic nodular goiter in both sisters. Several coincidental findings in nodular goiters and third ventricle colloid cysts retain our attention. Thyroglobulin secretory colloid cysts were responsible for these nodular goiters just as mucin colloid are for third ventricle cysts. This fact can be related to the same endodermal origin. Goiter is frequently encountered in a familial setting, especially in women. Due to the high prevalence of goiter in the normal population, a coincidental association with third ventricle colloid cysts remains possible. An intriguing feature is the development in patient 2 of symptomatic hyperprolactinemia present before surgery. Pituitary–hypothalamic abnormalities due to impaired cerebrospinal fluid (CSF) circulation have been previously reported. Perrone et al.  noted that basal and stimulated PRL levels were elevated in patients with shunts. In patients without shunts, basal PRL was normal, but peak PRL following TRH stimulation was elevated. In our patient, neither the prolactin dynamics, nor the absence of a pituitary lesion allowed the diagnosis of pituitary adenoma. However, fertility was only restored after dopaminergic treatment. Re-evaluation of hyperprolactinemia during pregnancy revealed more than 50% of heavy circulating forms of prolactin: this condition is recognised as macroprolactinemia. PRL heavy chains are currently known as big-big PRL (Prolactin and antibodies complex of 100 kDa) and big PRL (dimeric chains of prolactin of 45–60 kDa). These heavy forms
Table 2 Familial colloid cyst of the third ventricle: review of the literature Reference
Clinical associated condition
Identical twins Non twin brothers
Son Father Brother Sister Mother Two daughters
M M M M F F F M M M F F F F F F
Cataracts and retinal detachment
? ? ? 62 33 14 ? 28 68 25 41 41 36 33 28 38
Successful Successful Died 2 months later Successful Successful Deceased before surgery Successful Successful Successful Deceased before surgery Successful Deceased before surgery Successful No surgery Successful Successful
– Parkinson’s disease – – – – – – – – – – Goiter Goiter-Macroprolactinemia
H.V. Socin et al. / Clinical Neurology and Neurosurgery 104 (2002) 367–370
of PRL have a long lasting half-life. They can not cross through capillary walls . Incidence of macroprolactinemia has been calculated by Hattory as only 3% of all pregnancies .
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