Hernan Gonzalo Valdes Socin

Familial colloid cyst of the third ventricle: neuroendocrinological follow-up and review of the literature

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.

Comment on “Hypogonadotrophic hypogonadism due to a mutation in the luteinizing hormone β-subunit gene”

Correspondence to Hernan Valdes-Socin, M.D. Department of Endocrinology, University Hospital Center of Liège, University of Liège, Liège 4000, Belgium Tel: +32-43667083 Fax: +32-43667261 E-mail: hg.valdessocin@chu.ulg. ac.be Song et al. [1], report a new case of a homozygous p.Leu72Arg mutation in exon 3 of the luteinizing hormone β (LHB) gene leading to hypogonadism in a 19-year-old male patient, which is one of only a handful of cases reported to date. As more physicians become aware of diagnosing luteinizing hormone (LH) deficiency, an important point that remains unresolved is the issue of the best therapeutic strategy to offer to these patients. In patients with LHB mutations, the absence of LH during post-natal life leads to the characteristic pathological features seen on testicular biopsy, including immature Leydig cells, a reduction of Sertoli cells, hypomorphic seminiferous tubules, markedly decreased inhibin B, and low testicular volume. Although testosterone administration may induce virilization, it does not stimulate testicular development, as shown by Song et al. [1]. It has been suggested that gonadotropin treatment early after the diagnosis of hypogonadotropic hypogonadism may significantly improve the fertility potential of these patients through mimicking of the “mini puberty” state [2]. Our three male patients with documented LHB mutations that were treated with human chorionic gonadotropin (hCG) (Pregnyl, MSD, Brussels, Belgium) 5,000 IU/week for nearly 2 years had virilization and testicular growth, and spermatogenesis can occur, although it is usually suboptimal [3-5]. Our initial male patient successfully underwent assisted reproduction [4], and had recently a second child via the same method. Taking into account this experience and the available literature on this very rare disorder, we propose that young males with LH deficiency due to a documented LHB mutation should be initially treated with gonadotropins (hCG, recombinant LH) rather than testosterone, to promote Sertoli and Leydig maturation as well as to improve spermatogenesis and maximize the potential for fertility.

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor.

Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.

Persistent low levels of serum hCG due to heterophilic mouse antibodies: an unrecognized pitfall in the diagnosis of trophoblastic disease.

Abstract Phantom hCG refers to persistent mild elevations of hCG, leading physicians to unnecessary treatments whereas neither a true hCG nor a trophoblastic disease is present. We report the case of a 23-year-old woman with persistent low levels of serum hCG detected one month after miscarriage. As choriocarcinoma was suspected, a chemotherapy trial of methotrexate was prescribed, without any hCG reduction. Subsequently, laparoscopy ruled out a trophoblastic residue and the patient was referred to the Endocrine Unit for further investigations. While low levels of hCG were still detected in serum, no hCG was detected in the urine. In addition, when serum was processed in a HBT tube for revealing heterophilic antibodies, hCG was no longer detected. Such finding indicated the presence of phantom hCG due to heterophilic mouse antibodies interaction. This case raises the need of clinico-biological discussion to avoid inappropriate therapeutic decisions. Based on this case experience and after review of the literature, we suggest that current gynecological protocols for the diagnosis and treatment of trophoblastic disease should consider the inclusion of urinary hCG and/or a test for serum heterophilic antibodies when appropriate.

Asociacion de craneofaringioma y sindrome de Klinefelter en la transicion puberal : un desafio diagnostico

Craniopharyngioma is the most common pituitary tumor in childhood. It can compromise the pubertal development because of its evolution or treatment. Syndrome of Klinefelter is the most common cause of hipergonadotrophic hypogonadism in males. The concomitant presentation of both entities is extremely low (1/109) and the pathophysiological association is questionned. We present the case of a 18-year-old Belgian patient. He had a diagnosis of craniopharyngioma in childhood and he presented with panhypopituitarism after radiotherapy and surgical treatment. At the age of 14, he started pubertal induction with gonadotropin therapy without clinical response. Asociación de craneofaringioma y síndrome de Klinefelter en la transición puberal: un desafío diagnóstico Craniopharyngioma and Klinefelter syndrome during the pubertal transition: A diagnostic challenge A genetic evaluation confirmed a homogeneous 47, XXY karyotype. Failure of exogenous gonadotropin therapy revealed the hidden association of primary and secondary hypogonadism, demonstrating the importance of the followup and a multidisciplinary approach in these patients.

Gonadotropin secreting tumors

Most clinically nonfunctioning pituitary adenomas are gonadotropin-secreting adenomas, also termed gonadotropinomas.