TSH-secreting adenoma improved with cabergoline.

TSH-secreting adenomas are rare tumors, representing only 0.5 to 2.5% of pituitary adenomas. Their main clinical characteristics include signs of thyrotoxicosis, diffuse goiter and a compressive syndrome. Biologically, free T4 and T3 serum levels are elevated, contrasting with inadequate serum TSH levels and increased alpha chains. Magnetic resonance (MR) imaging shows a pituitary tumor, the main differential diagnosis being resistance to thyroid hormones. Treatment is based on surgery, possibly associated with somatostatin analogs and radiotherapy. Though the long-term evolution of this rare pathology seems to have improved, some clinical situations are still a challenge to treat. We report one such case that was resistant to both stereotactic radiotherapy and somatostatin analogs, but surprisingly improved with cabergoline. We suggest that cabergoline should be considered as an alternative treatment in cases of pituitary adenomas that resist traditional treatments.

Thyrotoxicosis revealing metastases of unrecognized thyroid cancer: a report on two cases.

We report two cases of thyrotoxicosis-revealing functional metastases of a follicular carcinoma that extended to the bones, liver and kidneys in one case and to the lungs in the other. Both patients had undergone surgical intervention for a thyroid nodule more than 15 years before the diagnosis of thyrotoxicosis and metastatic dissemination. In both the cases, the carcinoma was not recognized by the pathologist after the first surgical intervention, but was finally diagnosed several years later due to the occurrence of thyrotoxicosis. Iodine-131 therapy was effective at suppressing the thyrotoxicosis in both the patients. The effectiveness on the metastatic extension was very different for each patient: in the first case, the patient died a few years later without any control of the metastatic tissue. For the second patient, the metastases disappeared a few months after radioiodine treatment, with the patient still in remission more than 10 years later. The physiopathology and the evolution of these two cases are discussed with the data available in the literature.

Familial partial lipodystrophy due to the LMNA R482W mutation with multinodular goitre, extrapyramidal syndrome and primary hyperaldosteronism.

Objective To describe new data about the wide phenotypic variability of diseases due to mutations in the lamin A/C gene (LMNA). Design We report a complex phenotype in a patient with familial partial lipodystrophy of the Dunnigan type (FPLD) and study the frequency of her unusual clinical signs in 19 other LMNA-mutated lipodystrophic patients from 8 different families and 14 non-mutated family members. Case Report The patient was diagnosed with FPLD due to the R482W LMNA mutation after familial screening. Surprisingly, she had no biological signs of insulin resistance. The presence of hypertension with hypokalaemia led to the diagnosis of primary hyperaldosteronism. Thyroid investigations showed a euthyroid multinodular goiter. In addition, the patient exhibited a juvenile akineto-hypertonic syndrome. Results Goiter was identified with a similar frequency (55%) in LMNA-mutated lipodystrophic patients (11 out of 20, originating from 5 families among 8) compared to non-mutated family controls (35%; 5 patients out of 14, all originating from the same family). No case of primary hyperaldosteronism or extrapyramidal syndrome was identified in other studied subjects, either LMNA-mutated or not. Conclusions This R482W-LMNA mutated patient showed an association of features (primary hyperaldosteronism, euthyroid goiter and extra-pyramidal syndrome, raising the question of a link with her laminopathy. Prevalence of goiter tended to be higher in LMNA-mutated than in non-mutated subjects. Hyperaldosteronism seems coincidental. Although extrapyramidal syndrome has never been reported in lipodystrophic patients, it may nevertheless be linked to the LMNA mutation since multiple neurological features have been associated with alterations in lamins A/C.

[Calcium sensing receptor: physiology and pathology]. / Le récepteur sensible au calcium: physiologie et pathologie.

Calcium is a major ion in human metabolism and its level is highly controlled. This regulation is performed via the Calcium Sensing Receptor, a discovery which ten years ago led to the explanation of a number of clinical disorders. The syndromes caused by CaSR abnormalities are characterized by hypercalcemia or hypocalcemia, associated with inappropriate calciuria. An underlying genetic or auto-immune cause may be demonstrated. High blood calcium levels linked to mutations of the CaSR gene lead to familial hypocalciuric hypercalcemia and the neonatal and non neonatal forms with severe hypercalcemic. Hypocalcemia determined by mutations in the CaSR gene include autosomal dominant hypocalcemia and its sporadic form. Another clinical presentation similar to Bartter syndrome has been reported. Auto-antibodies directed against CaSRs, seen in auto-immune diseases, can lead to similar clinical presentations. Finally, CaSR polymorphisms modulate the range of blood calcium levels. With diagnosis of these diseases deleterious therapeutics can be avoided. The discovery of this receptor has led to new therapeutic prospects such as calcimimetics for hyperthyroidism.

[Monogenic severe insulin resistance syndromes]. / Syndromes d'insulinorésistance extrême génétiquement déterminés.

PURPOSE: To make a point about monogenic insulin resistance syndromes. CURRENT KNOWLEDGE AND KEY POINTS: Extreme insulin resistance syndromes are rare entities. The clinical and biological presentation is similar to that one of metabolic syndrome. Polycystic ovaries syndrome, non-alcoholic liver steatosis, acanthosis nigricans and overall, lipo-atrophic syndrome must be sought. Genetically determined forms are mainly linked to mutations of the insulin receptor gene and to lipoatrophic syndrome-linked mutations. The three syndromes related to mutations of the insulin receptor gene are Type A syndrome, first described by Kahn in young women, whereas leprechaunism and Rabson-Mendenhall syndromes are of neonatal onset. Main insulin resistance syndromes associated with lipo-atrophy are 1) Berardinelli-Seip or congenital generalized lipo-atrophic syndrome linked to mutations of seipin or AGPAT2 gene, 2) Dunnigan or partial familial lipoatrophic syndrome linked to mutations of lamin A/C, or sometimes PPAR gamma gene, and 3) acro-mandibular dysplasia and Köbberling syndrome. FUTURE PROSPECTS AND PROJECTS: In conclusion, an early onset of insulin resistance, especially in association with lipodystrophy must suggest a monogenic insulin resistance syndrome. Outstanding advances in insulin resistance pheno- and genotype identification, despite incomplete yet, offers a better understanding of insulin resistance, atherosclerosis and ageing mechanisms, that should lead to therapeutic improvement.