Kirsten Reschke

Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2

BACKGROUND Head and neck paragangliomas (HNPs) occur as sporadic or familial entities, the latter mostly in association with germline mutations of the SDHB, SDHC, or SDHD (SDHx) genes. Heritable non-SDHx HNP might occur in von Hippel-Lindau disease (VHL, VHL gene), multiple endocrine neoplasia type 2 (MEN2, RET gene), and neurofibromatosis type 1 (NF1, NF1 gene). Reports of non-SDHx HNP presentations are scarce and guidance for genetic testing nonexistent. PATIENTS AND METHODS An international consortium registered patients with HNPs and performed mutation analyses of the SDHx, VHL, and RET genes. Those with SDHx germline mutations were excluded for purposes of this study. Personal and family histories were evaluated for paraganglial tumors, for the major tumor manifestations, and for family history of VHL, MEN2, or NF1. RESULTS Twelve patients were found to have hereditary non-SDHx HNPs of a total of 809 HNP and 2084 VHL registrants, 11 in the setting of germline VHL mutations and one of a RET mutation. The prevalence of hereditary HNP is five in 1000 VHL patients and nine in 1000 non-SDHx HNP patients. Comprehensive literature review revealed previous reports of HNPs in five VHL, two MEN2, and one NF1 patient. Overall, 11 here presented HNP cases, and four previously reported VHL-HNPs had lesions characteristic for VHL and/or a positive family history for VHL. CONCLUSIONS Our observations provide evidence that molecular genetic testing for VHL or RET germline mutations in patients with HNP should be done only if personal and/or family history shows evidence for one of these syndromes.

Manifestation eines Cushing-Syndroms und osteoporotischer Frakturen in der Schwangerschaft einer Patientin mit Carney-Komplex

ZusammenfassungAnamnese und klinischer Befund: Aufgrund von therapierefraktären Lendenwirbelsäulenbeschwerden wurde bein einer 31-jährigen Patientin nach einer Sectio caesarea eine Röntgenuntersuchung veranlasst, die Frakturen von L2 und L3 bei stark erhöhter Strahlentransparenz zeigte. Neben den klinischen Zeichen des Hypercortisolismus waren bei der Untersuchung auch zahlreiche Hyperpigmentationen im Gesichtsbereich unter Einbeziehung des Lippenrots und der rechten Konjunktiva auffällig, so dass ein Carney-Komplex vermutet wurde. Untersuchungen: Ein nicht supprimierbares Cortisol bestätigte in der endokrinologischen Diagnostik einen Hypercortisolismus. Die selektive Venenkatheteruntersuchung ergab den Verdacht auf eine bilaterale Cortisolmehrproduktion. Auch in der CT-Untersuchung der Nebennieren fanden sich knotige Veränderungen rechts und eine Hyperplasie links. Therapie und Verlauf: Bei der bilateralen Adrenalektomie konnte histologisch die Verdachtsdiagnose einer primär pigmentierten nodulären Hyperplasie bestätigt werden. Die Zeichen des Hypercortisolismus bildeten sich rasch zurück. Schlussfolgerung: Die Diagnose eines Cushing-Syndroms bei Carney-Komplex wurde bei unserer Patientin erst nach Beendigung der Schwangerschaft gestellt, obgleich die Zeichen des Hypercortisolismus schon lange vor Beginn der Schwangerschaft bestanden. An die seltene Diagnose eines Carney-Komplexes sollte bei klinischen Symptomen des Hypercortisolismus und charakteristischen phänotypischen Veränderungen (Hyperpigmentationen) gedacht werden.AbstractHistory and Clinical Findings: In a 31-year-old patient a conventional X-ray was performed due to persistend pain at the lumbar spine level after a cesarean section. It revealed compression fractures of L2 and L3. Besides very clear clinical signs of hypercortisolism, multiple hyperpigmentations and naevi in the patients face including the lips and the conjunctiva of the right eye were visible, suggesting a Carney complex. Investigations: Insuppressible cortisol levels confirmed an adrenal origin of hypercortisolism. A selective catheterization of adrenal veins supported the presence of bilateral adrenal cortisol production. The computed tomography showed nodular lesions in the right and a hyperplasia of the left adrenal gland. Treatment and Course: A bilateral adrenalectomy was performed and a primary pigmented nodular adrenal hyperplasia was confirmed histologically. Clinical signs of hypercortisolism rapidly resolved after adrenalectomy. Conclusions: The diagnosis of Cushings syndrome as a part of Carney complex was diagnosed at the end of a pregnancy although signs of hypercortisolism were present a long time before. The rare diagnosis of Carney complex should be considered in patients exhibiting symptoms of hypercortisolism and the typical clinical signs (hyperpigmentations).

Effects of Intracerebroventricularly and Intraperitoneally Administered Growth Hormone on Body Weight and Food Intake in fa/fa Zucker Rats

Growth hormone (GH) possesses multiple metabolic effects, in particular with regard to glucose and lipid homeostasis. Studies on the effects of GH on body weight and food and water intake are scarce and have yielded controversial results. We investigated the effects of different modes of GH administration on the parameters of body weight and food intake as well as on insulin and leptin concentrations in fa/fa Zucker rats. In control experiments, aqua pro injectione was given. GH was administered over a time period of 11 days at a daily dose of 250 µg intraperitoneally (i.p.) and 25 µg intracerebroventricularly (i.c.v.). While both food intake and body weight were found to be unaltered in the four groups after this observation period, there was an enhanced food intake and consecutively an increase in body weight over the day period when compared to the night period in the groups of rats that received GH i.c.v. or i.p. This tendency was also shown for water intake. Insulin and leptin concentrations were similar in all groups. Thus, injection of GH appears to modify food intake-related behavior, since the periods of enhanced food and water intake were shifted from night- to daytime. Thus, while in general the metabolic parameters remained unchanged, the activity pattern was clearly modified.

Carney Complex – An Unexpected Finding during Puerperium

Carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with Carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing’s syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of Obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L2/L3 with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing’s syndrome, it was recognized that the patient met the diagnostic criteria for Carney complex.

Obesity: sometimes more than adipose tissue

the liver. Only a few ovarian tumours appear cystic at sonography. The tumour marker CA 125 was 426 U/mL (normal range: <35 U/mL). The patient was transferred to our surgical department. Extirpation of the tumour and bilateral oophoro-salpingo-hysterectomy was done. A giant tumour with greatest diameter 40 cm weighing 26 Kg was removed, mostly containing chocolate-like fluid. Histology showed it to be a cystadenoma of the right ovary with an intact capsule. To our knowledge, a tumour of this size has only very rarely been encountered. Within this cystadenoma, there was a moderately differentiated adenocarcinoma of the ovary with greatest diameter of 10 cm. The carcinoma had developed within the cystadenoma, without invading the capsule. The contralateral ovary was tumour-free, the uterus had a leiomyoma of 1·5 cm diameter. There were no perioperative complications. Bear the unlikely in mind, even when confronted with seemingly straightforward, common conditions such as obesity.